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Sample records for severe interstitial fibrosis

  1. Phosphocalcic Markers and Calcification Propensity for Assessment of Interstitial Fibrosis and Vascular Lesions in Kidney Allograft Recipients.

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    Lena Berchtold

    Full Text Available Renal interstitial fibrosis and arterial lesions predict loss of function in chronic kidney disease. Noninvasive estimation of interstitial fibrosis and vascular lesions is currently not available. The aim of the study was to determine whether phosphocalcic markers are associated with, and can predict, renal chronic histological changes. We included 129 kidney allograft recipients with an available transplant biopsy in a retrospective study. We analyzed the associations and predictive values of phosphocalcic markers and serum calcification propensity (T50 for chronic histological changes (interstitial fibrosis and vascular lesions. PTH, T50 and vitamin D levels were independently associated to interstitial fibrosis. PTH elevation was associated with increasing interstitial fibrosis severity (r = 0.29, p = 0.001, while T50 and vitamin D were protective (r = -0.20, p = 0.025 and r = -0.23, p = 0.009 respectively. On the contrary, fibroblast growth factor 23 (FGF23 and Klotho correlated only modestly with interstitial fibrosis (p = 0.045 whereas calcium and phosphate did not. PTH, vitamin D and T50 were predictors of extensive fibrosis (AUC: 0.73, 0.72 and 0.68 respectively, but did not add to renal function prediction. PTH, FGF23 and T50 were modestly predictive of low fibrosis (AUC: 0.63, 0.63 and 0.61 but did not add to renal function prediction. T50 decreased with increasing arterial lesions (r = -0.21, p = 0.038. The discriminative performance of T50 in predicting significant vascular lesions was modest (AUC 0.61. In summary, we demonstrated that PTH, vitamin D and T50 are associated to interstitial fibrosis and vascular lesions in kidney allograft recipients independently of renal function. Despite these associations, mineral metabolism indices do not show superiority or additive value to fibrosis prediction by eGFR and proteinuria in kidney allograft recipients, except for vascular lesions where T50 could be of relevance.

  2. Familial Interstitial Pulmonary Fibrosis: A Large Family with Atypical Clinical Features

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    Ranji Chibbar

    2010-01-01

    Full Text Available A large kindred of familial pulmonary fibrosis is reported. Six members from the first two generations of this particular kindred were described more than 40 years previously; six more individuals from the third and fourth generations have also been evaluated. The proband, now 23 years of age, has mild disease; the other 11 documented affected family members all died from their disease at an average age of 37 years (range 25 to 50 years. The pathology was that of usual interstitial pneumonia, as is typical in idiopathic pulmonary fibrosis. However, the initial radiographic pattern in many of these individuals was upper lobe and nodular and, along with the young age, was atypical for idiopathic pulmonary fibrosis. Several genetic abnormalities have been associated with familial pulmonary fibrosis. The present study examined the genes coding for surfactant protein-C, ATP-binding cassette protein A3 and telomerase, and found no abnormalities.

  3. Airway-centered interstitial fibrosis: etiology, clinical findings and prognosis.

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    Kuranishi, Lilian Tiemi; Leslie, Kevin O; Ferreira, Rimarcs Gomes; Coletta, Ester Aparecida Ney; Storrer, Karin Mueller; Soares, Maria Raquel; de Castro Pereira, Carlos Alberto

    2015-05-09

    Airway-centered Interstitial Fibrosis (ACIF) is a common pathologic pattern observed in our practice. The objectives of this study are to describe the causes associated with ACIF in a large sample of patients and its effect on survival. A retrospective study in three centers of interstitial lung disease in São Paulo, between January of 1995 and December of 2012. The surgical lung biopsy specimens were reviewed by three pathologists. The clinical, functional and tomographic findings were analyzed by a standardized protocol. There were 68 cases of ACIF, most of them women. The mean age was 57 ± 12 yr. Dyspnea, cough, restrictive pattern at spirometry and oxygen desaturation at exercise were common. A reticular pattern with peribronchovascular infiltrates was found in 79% of the cases. The etiologies of ACIF were hypersensitivity pneumonitis in 29 (42.6%), gastroesophageal reflux disease in 17 (25.0%), collagen vascular disease in 4 (5.9%), a combination of them in 15 cases and idiopathic in 3 (4.4%). The median survival was 116 months (95% CI = 58.5 - 173.5). Lower values of oxygen saturation at rest, presence of cough and some histological findings--organizing tissue in the airways, fibroblastic foci and microscopic honeycombing--were predictors of worse survival. ACIF is an interstitial lung disease with a better survival when compared with IPF. The main etiologies are HP and GERD. The oxygen saturation at rest, the presence of cough and some histological findings are predictors of survival.

  4. Correlation of pulmonary function and usual interstitial pneumonia computed tomography patterns in idiopathic pulmonary fibrosis.

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    Arcadu, Antonella; Byrne, Suzanne C; Pirina, Pietro; Hartman, Thomas E; Bartholmai, Brian J; Moua, Teng

    2017-08-01

    Little is known about presenting 'inconsistent' or 'possible' usual interstitial pneumonia (UIP) computed tomography (CT) patterns advancing to 'consistent' UIP as disease progresses in idiopathic pulmonary fibrosis (IPF). We hypothesized that if 'consistent' UIP represented more advanced disease, such a pattern on presentation should also correlate with more severe pulmonary function test (PFT) abnormalities. Consecutive IPF patients (2005-2013) diagnosed by international criteria with baseline PFT and CT were included. Presenting CTs were assessed by three expert radiologists for consensus UIP pattern ('consistent', 'possible', and 'inconsistent'). Approximation of individual and combined interstitial abnormalities was also performed with correlation of interstitial abnormalities and UIP CT pattern made with PFT findings and survival. Three-hundred and fifty patients (70% male) were included with a mean age of 68.3 years. Mean percent predicted forced vital capacity (FVC%) and diffusion capacity (DLCO%) was 64% and 45.5% respectively. Older age and male gender correlated more with 'consistent' UIP CT pattern. FVC% was not associated with any UIP pattern but did correlate with total volume of radiologist assessed interstitial abnormalities. DLCO% was lower in those with 'consistent' UIP pattern. A 'consistent' UIP CT pattern was also not independently predictive of survival after correction for age, gender, FVC%, and DLCO%. PFT findings appear to correlate with extent of radiologic disease but not specific morphologic patterns. Whether such UIP patterns represent different stages of disease severity or radiologic progression is not supported by coinciding pulmonary function decline. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Fanconi's syndrome, interstitial fibrosis and renal failure by aristolochic acid in Chinese herbs.

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    Hong, Yin-Tai; Fu, Lin-Shien; Chung, Lin-Huei; Hung, Shien-Chung; Huang, Yi-Ting; Chi, Chin-Shiang

    2006-04-01

    Aristolochic acid-associated nephropathy (AAN) has been identified as a separate entity of progressive tubulo-interstitial nephropathy. Its characteristic pathological findings, including hypocellular interstitial fibrosis, intimal thickening of interlobular and afferent arterioles with glomeruli sparing or mild sclerosis, have been identified. Many cases of AAN in adults have been reported in Taiwan as well as throughout the world, but it has seldom been described in children. We report on a 10-year-old boy who presented with severe anemia, Fanconi's syndrome, and progressive renal failure. Renal biopsy revealed typical findings of AAN. Aristolochic acids I and II were identified from a Chinese herb mixture ingested by the boy. AAN was diagnosed after other etiologies had been excluded. The case demonstrates the hazards of Chinese herbs with regard to children's health in Taiwan and suggests that more attention should be paid to this issue.

  6. Acute lyme infection presenting with amyopathic dermatomyositis and rapidly fatal interstitial pulmonary fibrosis: a case report

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    Nguyen Hanh

    2010-06-01

    Full Text Available Abstract Introduction Dermatomyositis has been described in the setting of lyme infection in only nine previous case reports. Although lyme disease is known to induce typical clinical findings that are observed in various collagen vascular diseases, to our knowledge, we believe that our case is the first presentation of acute lyme disease associated with amyopathic dermatomyositis, which was then followed by severe and fatal interstitial pulmonary fibrosis only two months later. Case presentation We present a case of a 64-year-old African-American man with multiple medical problems who was diagnosed with acute lyme infection after presenting with the pathognomonic rash and confirmatory serology. In spite of appropriate antimicrobial therapy for lyme infection, he developed unexpected amyopathic dermatomyositis and then interstitial lung disease. Conclusions This case illustrates a potential for lyme disease to produce clinical syndromes that may be indistinguishable from primary connective tissue diseases. An atypical and sequential presentation (dermatomyositis and interstitial lung disease of a common disease (lyme infection is discussed. This case illustrates that in patients who are diagnosed with lyme infection who subsequently develop atypical muscular, respiratory or other systemic complaints, the possibility of severe rheumatological and pulmonary complications should be considered.

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

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    Jia Cuiying

    2008-01-01

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

  8. Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

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    Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

    2015-01-01

    The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

  9. Diffuse interstitial fibrosis assessed by cardiac magnetic resonance is associated with dispersion of ventricular repolarization in patients with hypertrophic cardiomyopathy

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    David Hurtado-de-Mendoza, MD

    2017-06-01

    Conclusion: Diffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1–V4.

  10. Interstitial lung diseases with fibrosis - the pattern at high resolution

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    Jarzemska, A.; Lasek, W.; Nawrocka, E.; Meder, G.; Zapala, M.

    2003-01-01

    Surgical lung biopsy, either open thoracotomy or video-assisted thoracoscopy is recommended in the diagnosis of interstitial lung diseases (ILD). In some cases, however, the repetitive pattern of radiological features in high-resolution computed tomography is often sufficient to confirm the diagnosis in a non-invasive manner. The purpose of the study was to determine whether patients with ILD can be selected on the basis of the HRCT pattern. Thin-section CT scans were performed in 40 patients with histologically proven idiopathic interstitial pneumonia (26 patients with usual interstitial pneumonia UIP, 2 patients with desquamative interstitial pneumonia DIP, 2 patients with bronchiolitis obliterans organizing pneumonia BOOP, 2 patients with non-specific interstitial pneumonia NSIP, 11 patients with hypersensitivity pneumonitis, and 3 patients with pulmonary histiocytosis X). The location and the intensity of lesions were taken into consideration. Clinical and histopathological findings were compared. HRCT features of interstitial lung diseases such as nodules and cystic spaces in hypersensitivity pneumonitis and pulmonary histiocytosis, and ground-glass opacities in idiopathic interstitial pneumonias (IIP) were statistically significant for differential diagnosis in ILD cases. Combination of honeycombing and ground-glass opacities found in UIP and nodules found in DIP were also statistically significant features in IIP subtypes diagnosis. In some cases, HRCT patterns of hypersensitivity pneumonitis, pulmonary histiocytosis X and IPF combined with clinical findings allowed for the accurate diagnosis without resorting to lung biopsy. Within a group of idiopathic interstitial pneumonia only in usual interstitial pneumonia characteristic pattern in thin-section CT can be defined. In other subgroups some typical features can imply a diagnosis. (author)

  11. Chronic pulmonary interstitial fibrosis in a blue-fronted Amazon parrot (Amazona aestiva aestiva).

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    Amann, Olga; Kik, Marja J L; Passon-Vastenburg, Maartje H A C; Westerhof, Ineke; Lumeij, Johannes T; Schoemaker, Nico J

    2007-03-01

    A 30-yr-old blue-fronted Amazon parrot (Amazon aestiva aestiva) was presented to the clinic with a history of sneezing more often during the last 2 mo. Physical examination revealed only a mild nasal discharge. Complete hematologic and plasma biochemical examination showed no abnormalities. Computerized tomography (CT) of the complete bird showed generalized lung alterations consistent with lung fibrosis. Two lung biopsies were taken. The results of the histologic examination of the biopsies confirmed the tentative CT diagnosis of pulmonary interstitial fibrosis. To our knowledge this is the first reported case of chronic pulmonary interstitial fibrosis diagnosed by means of a lung biopsy in an avian species. The histologic characteristics are discussed and compared with those of human idiopathic pulmonary fibrosis.

  12. Myostatin induces interstitial fibrosis in the heart via TAK1 and p38.

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    Biesemann, Nadine; Mendler, Luca; Kostin, Sawa; Wietelmann, Astrid; Borchardt, Thilo; Braun, Thomas

    2015-09-01

    Myostatin, a member of the TGF-β superfamily of secreted growth factors, is a negative regulator of skeletal muscle growth. In the heart, it is expressed at lower levels compared to skeletal muscle but up-regulated under disease conditions. Cre recombinase-mediated inactivation of myostatin in adult cardiomyocytes leads to heart failure and increased mortality but cardiac function of surviving mice is restored after several weeks probably due to compensatory expression in non-cardiomyocytes. To study long-term effects of increased myostatin expression in the heart and to analyze the putative crosstalk between cardiomyocytes and fibroblasts, we overexpressed myostatin in cardiomyocytes. Increased expression of myostatin in heart muscle cells caused interstitial fibrosis via activation of the TAK-1-MKK3/6-p38 signaling pathway, compromising cardiac function in older mice. Our results uncover a novel role of myostatin in the heart and highlight the necessity for tight regulation of myostatin to maintain normal heart function.

  13. Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis.

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    Ding, Hao; Jiang, Lei; Xu, Jing; Bai, Feng; Zhou, Yang; Yuan, Qi; Luo, Jing; Zen, Ke; Yang, Junwei

    2017-09-01

    Chronic kidney diseases generally lead to renal fibrosis. Despite great progress having been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear, and so far no effective therapeutic antifibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis. Both gene and protein assay showed that the expression of glycolysis enzymes was upregulated in mouse kidneys with unilateral ureter obstruction (UUO) surgery or in transforming growth factor-β1 (TGF-β1)-treated renal interstitial fibroblasts. Aerobic glycolysis flux, indicated by glucose uptake and lactate production, was increased in mouse kidney with UUO nephropathy or TGF-β1-treated renal interstitial fibroblasts and positively correlated with fibrosis process. In line with this, we found that increasing aerobic glycolysis can remarkably induce myofibroblast activation while aerobic glycolysis inhibitors shikonin and 2-deoxyglucose attenuate UUO-induced mouse renal fibrosis and TGF-β1-stimulated myofibroblast activation. Furthermore, mechanistic study indicated that shikonin inhibits renal aerobic glycolysis via reducing phosphorylation of pyruvate kinase type M2, a rate-limiting glycolytic enzyme associated with cell reliance on aerobic glycolysis. In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy. Copyright © 2017 the American Physiological Society.

  14. Radiographic and high resolution CT findings of non-specific interstitial pneumonia/fibrosis

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    Kondoh, Yasuhiro; Taniguchi, Hiroyuki; Nishiyama, Satoshi [Tosei General Hospital, Seto, Aichi (Japan); Yokoi, Toyoharu; Suzuki, Ryujiro; Noda, Yasunobu; Kato, Toshiyuki; Kaneko, Michie

    1999-01-01

    We evaluated the radiographic and high resolution CT findings in fifteen patients with biopsy proven nonspecific interstitial pneumonia. The most common radiographic findings in NSIP were bilateral infiltrates involving alveolar pattern, interstitial pattern, and mixed alveolar-interstitial pattern, which distributed mainly in the middle and lower lung zones. Loss of lung volumes were common. The predominant findings of linear and reticular opacities on HRCT were peribronchovascular interstitial thickening, parenchymal bands, intralobular interstitial thickening, and traction bronchiectasis. Honeycombing was not noted in any patient on initial CT scans. The predominant findings of increased lung opacity were mixed pattern of ground glass opacity and consolidation. Because these findings mimic those of idiopathic pulmonary fibrosis/usual interstitial pneumonia, distinction between NSIP and IPF/UIP seems to be difficult by radiographic and HRCT findings. The response to corticosteroid therapy was good. At follow up HRCT, the pulmonary abnormalities observed on initial scans had disappeared or were diminished in most cases. Intralobular interstitial thickening and traction bronchiectasis, that have been considered to be an indicator of irreversible fibrosis, occasionally disappeared after corticosteroid therapy. (author)

  15. [Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

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    Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

    2014-09-15

    Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  16. Follistatin, an Activin Antagonist, Ameliorates Renal Interstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

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    Akito Maeshima

    2014-01-01

    Full Text Available Activin, a member of the TGF-β superfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO. The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitial α-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression of α-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression.

  17. Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis.

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    Geng, Jie-jie; Zhang, Kui; Chen, Li-na; Miao, Jin-lin; Yao, Meng; Ren, Ying; Fu, Zhi-guang; Chen, Zhi-nan; Zhu, Ping

    2014-09-01

    Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Coal Mine Dust Desquamative Chronic Interstitial Pneumonia: A Precursor of Dust-Related Diffuse Fibrosis and of Emphysema

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    Tomislav M Jelic

    2017-07-01

    Full Text Available Background: Diseases associated with coal mine dust continue to affect coal miners. Elucidation of initial pathological changes as a precursor of coal dust-related diffuse fibrosis and emphysema, may have a role in treatment and prevention. Objective: To identify the precursor of dust-related diffuse fibrosis and emphysema. Methods: Birefringent silica/silicate particles were counted by standard microscope under polarized light in the alveolar macrophages and fibrous tissue in 25 consecutive autopsy cases of complicated coal worker's pneumoconiosis and in 21 patients with tobacco-related respiratory bronchiolitis. Results: Coal miners had 331 birefringent particles/high power field while smokers had 4 (p<0.001. Every coal miner had intra-alveolar macrophages with silica/silicate particles and interstitial fibrosis ranging from minimal to extreme. All coal miners, including those who never smoked, had emphysema. Fibrotic septa of centrilobular emphysema contained numerous silica/silicate particles while only a few were present in adjacent normal lung tissue. In coal miners who smoked, tobacco-associated interstitial fibrosis was replaced by fibrosis caused by silica/silicate particles. Conclusion: The presence of silica/silicate particles and anthracotic pigment-laden macrophages inside the alveoli with various degrees of interstitial fibrosis indicated a new disease: coal mine dust desquamative chronic interstitial pneumonia, a precursor of both dust-related diffuse fibrosis and emphysema. In studied coal miners, fibrosis caused by smoking is insignificant in comparison with fibrosis caused by silica/silicate particles. Counting birefringent particles in the macrophages from bronchioalveolar lavage may help detect coal mine dust desquamative chronic interstitial pneumonia, and may initiate early therapy and preventive measures.

  19. Coal Mine Dust Desquamative Chronic Interstitial Pneumonia: A Precursor of Dust-Related Diffuse Fibrosis and of Emphysema.

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    Jelic, Tomislav M; Estalilla, Oscar C; Sawyer-Kaplan, Phyllis R; Plata, Milton J; Powers, Jeremy T; Emmett, Mary; Kuenstner, John T

    2017-07-01

    Diseases associated with coal mine dust continue to affect coal miners. Elucidation of initial pathological changes as a precursor of coal dust-related diffuse fibrosis and emphysema, may have a role in treatment and prevention. To identify the precursor of dust-related diffuse fibrosis and emphysema. Birefringent silica/silicate particles were counted by standard microscope under polarized light in the alveolar macrophages and fibrous tissue in 25 consecutive autopsy cases of complicated coal worker's pneumoconiosis and in 21 patients with tobacco-related respiratory bronchiolitis. Coal miners had 331 birefringent particles/high power field while smokers had 4 (pcoal miner had intra-alveolar macrophages with silica/silicate particles and interstitial fibrosis ranging from minimal to extreme. All coal miners, including those who never smoked, had emphysema. Fibrotic septa of centrilobular emphysema contained numerous silica/silicate particles while only a few were present in adjacent normal lung tissue. In coal miners who smoked, tobacco-associated interstitial fibrosis was replaced by fibrosis caused by silica/silicate particles. The presence of silica/silicate particles and anthracotic pigment-laden macrophages inside the alveoli with various degrees of interstitial fibrosis indicated a new disease: coal mine dust desquamative chronic interstitial pneumonia, a precursor of both dust-related diffuse fibrosis and emphysema. In studied coal miners, fibrosis caused by smoking is insignificant in comparison with fibrosis caused by silica/silicate particles. Counting birefringent particles in the macrophages from bronchioalveolar lavage may help detect coal mine dust desquamative chronic interstitial pneumonia, and may initiate early therapy and preventive measures.

  20. Ultrasound lung comets: new echographic sign of lung interstitial fibrosis in systemic sclerosis

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    C. Giacomelli

    2011-09-01

    Full Text Available Objective: Interstitial lung disease (ILD and pulmonary arterial hypertension (PAH are common complications of systemic sclerosis (SSc. Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC, i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILaD and PAH by integrated cardiac and chest ultrasound in SSc. Methods: We enrolled 30 consecutive SSc patients (age= 54±13 years, 23 females in the Rheumatology Clinic of Pisa University. In all, we assessed systolic pulmonary arterial pressure (SPAP, from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space. All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70, and antiicentromere associated with development of pulmonary involvement. Twenty-eight patients also underwent high resolution computed tomography, HRCT (from 0= no fibrosis to 3= honey combing. Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence Scl-70 antibodies. ULC number was similar in localized or diffuse forms (16±20 vs 21±19, p=ns and was unrelated to SPAP (r=0.216, p=ns. Conclusions: Chest sonography assessment and ULC allow a complete, simple, radiation-free characterization of interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies.

  1. Tranilast prevents renal interstitial fibrosis by blocking mast cell infiltration in a rat model of diabetic kidney disease.

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    Yin, Dan-Dan; Luo, Jun-Hui; Zhao, Zhu-Ye; Liao, Ying-Jun; Li, Ying

    2018-05-01

    Renal interstitial fibrosis is a final pathway that is observed in various types of kidney diseases, including diabetic kidney disease (DKD). The present study investigated the effect of tranilast on renal interstitial fibrosis and the association between its role and mast cell infiltration in a rat model of DKD. A total of 30 healthy 6‑week‑old male Sprague‑Dawley rats were randomly divided into the following four groups: Normal control group; DKD model group; low‑dose tranilast group (200 mg/kg/day); and high‑dose tranilast group (400 mg/kg/day). The morphological alterations of tubulointerstitial fibrosis were evaluated by Masson's trichrome staining, while mast cell infiltration into the renal tubular interstitium was measured by toluidine blue staining and complement C3a receptor 1 (C3aR) immunohistochemical staining (IHC). The expression of fibronectin (FN), collagen I (Col‑I), stem cell factor (SCF) and proto‑oncogene c‑kit (c‑kit) was detected by IHC, western blotting and reverse transcription‑quantitative‑polymerase chain reaction. The results demonstrated that tubulointerstitial fibrosis and mast cell infiltration were observed in DKD model rats, and this was improved dose‑dependently in the tranilast treatment groups. The expression of FN, Col‑I, SCF and c‑kit mRNA and protein was upregulated in the tubulointerstitium of DKD model rats compared with the normal control rats, and tranilast inhibited the upregulated expression of these markers. Furthermore, the degree of SCF and c‑kit expression demonstrated a significant positive correlation with C3aR‑positive mast cells and the markers of renal interstitial fibrosis. The results of the present study indicate that mast cell infiltration may promote renal interstitial fibrosis via the SCF/c‑kit signaling pathway. Tranilast may prevent renal interstitial fibrosis through inhibition of mast cell infiltration mediated through the SCF/c-kit signaling pathway.

  2. Distribution and components of interstitial inflammation and fibrosis in IgG4-related kidney disease: analysis of autopsy specimens.

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    Hara, Satoshi; Kawano, Mitsuhiro; Mizushima, Ichiro; Harada, Kenichi; Takata, Takuma; Saeki, Takako; Ubara, Yoshifumi; Sato, Yasuharu; Nagata, Michio

    2016-09-01

    IgG4-related kidney disease (IgG4-RKD) occasionally progresses to chronic renal failure and is pathologically characterized by IgG4-positive lymphoplasmacyte-rich tubulointerstitial nephritis with storiform fibrosis (bird's-eye pattern fibrosis). Although radiology reveals a heterogeneous distribution of affected areas in this disease, their true distribution within the whole kidney is still unknown because of difficulty in estimating this from needle biopsy samples. Using 5 autopsy specimens, the present study histologically characterized the distribution and components of interstitial inflammation and fibrosis in IgG4-RKD. Interstitial lymphoplasmacytic infiltration or fibrosis was observed in a variety of anatomical locations such as intracapsular, subcapsular, cortical, perivascular, and perineural regions heterogeneously in a patchy distribution. They tended to be more markedly accumulated around medium- and small-sized vessels. Storiform fibrosis was limited to the cortex. Immunostaining revealed nonfibrillar collagens (collagen IV and VI) and fibronectin predominance in the cortical lesion, including storiform fibrosis. In contrast, fibril-forming collagens (collagen I and III), collagen VI, and fibronectin were the main components in the perivascular lesion. In addition, α-smooth muscle actin-positive myofibroblasts were prominently accumulated in the early lesion and decreased with progression, suggesting that myofibroblasts produce extracellular matrices forming a peculiar fibrosis. In conclusion, perivascular inflammation or fibrosis of medium- and small-sized vessels is a newly identified pathologic feature of IgG4-RKD. Because storiform fibrosis contains mainly nonfibrillar collagens, "interstitial fibrosclerosis" would be a suitable term to reflect this. The relation between the location and components of fibrosis determined in whole kidney samples provides new clues to the pathophysiology underlying IgG4-RKD. Copyright © 2016 The Authors. Published

  3. Immune complexes, gallium lung scans, and bronchoalveolar lavage in idiopathic interstitial pneumonitis-fibrosis

    International Nuclear Information System (INIS)

    Gelb, A.F.; Dreisen, R.B.; Epstein, J.D.; Silverthorne, J.D.; Bickel, Y.; Fields, M.; Border, W.A.; Taylor, C.R.

    1983-01-01

    We obtained results of lung immune complexes (LIC), circulating immune complexes (CIC), 48-hour gallium lung scans (scans), bronchoalveolar lavage (BAL), and pulmonary function tests in 20 patients with idiopathic interstitial pneumonitis-fibrosis. Sixteen patients had predominantly interstitial (13 cases UIP) and/or intraalveolar (3 cases DIP) cellular disease (group 1). Prior to corticosteroid therapy in group 1, scans were positive in 75 percent, CIC were elevated in 86 percent, LIC were present in 64 percent, and BAL was abnormal in 90 percent. Duration of follow-up after treatment was 3.5 +/- 1.0 year. In group 1 after treatment with corticosteroids in 13 patients and corticosteroids and penicillamine (three patients) and plasmapheresis (one patient), only four patients remain stable or improved. After corticosteroid therapy, elevated CIC returned to normal values despite progressive patient deterioration. In three patients, lung immune complexes were still detected after circulating immune complexes had returned to normal after corticosteroid therapy. In group 2 were four patients with fibrotic disease; scans and CIC were uniformly negative, LIC were weakly present in only one patient, and BAL was abnormal in all. Despite corticosteroid therapy, all have died or deteriorated. These results suggest that positive gallium lung scans, BAL, circulating immune complexes, and to a lesser extent, lung immune complexes are associated with the cellular phase of interstitial pneumonia, but do not reliably identify a corticosteroid-responsive group

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

    Science.gov (United States)

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

    2016-06-03

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

  5. Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis.

    Science.gov (United States)

    Juge, Pierre-Antoine; Borie, Raphaël; Kannengiesser, Caroline; Gazal, Steven; Revy, Patrick; Wemeau-Stervinou, Lidwine; Debray, Marie-Pierre; Ottaviani, Sébastien; Marchand-Adam, Sylvain; Nathan, Nadia; Thabut, Gabriel; Richez, Christophe; Nunes, Hilario; Callebaut, Isabelle; Justet, Aurélien; Leulliot, Nicolas; Bonnefond, Amélie; Salgado, David; Richette, Pascal; Desvignes, Jean-Pierre; Lioté, Huguette; Froguel, Philippe; Allanore, Yannick; Sand, Olivier; Dromer, Claire; Flipo, René-Marc; Clément, Annick; Béroud, Christophe; Sibilia, Jean; Coustet, Baptiste; Cottin, Vincent; Boissier, Marie-Christophe; Wallaert, Benoit; Schaeverbeke, Thierry; Dastot le Moal, Florence; Frazier, Aline; Ménard, Christelle; Soubrier, Martin; Saidenberg, Nathalie; Valeyre, Dominique; Amselem, Serge; Boileau, Catherine; Crestani, Bruno; Dieudé, Philippe

    2017-05-01

    Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT , RTEL1 , PARN or SFTPC coding regions . The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT , RTEL1 , PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10 -4 ). Telomeres were shorter in RA-ILD patients with a TERT , RTEL1 or PARN mutation than in controls (p=2.87×10 -2 ).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility. Copyright ©ERS 2017.

  6. CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.

    Science.gov (United States)

    Meziani, Lydia; Mondini, Michele; Petit, Benoît; Boissonnas, Alexandre; Thomas de Montpreville, Vincent; Mercier, Olaf; Vozenin, Marie-Catherine; Deutsch, Eric

    2018-03-01

    Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration.We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation.High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate. Bronchoalveolar lavage demonstrated upregulation of both types of cytokines. At steady state, tissue-infiltrating macrophages (IMs) expressed 10-fold more arginase (Arg)-1 than alveolar macrophages (AMs), and a 40-fold upregulation of Arg-1 was found in IMs isolated from RIF. IMs, but not AMs, were able to induce myofibroblast activation in vitro In addition, whereas depletion of AMs using Clodrosome didn't affect RIF score, depletion of IMs using a clinically available colony-stimulating factor receptor-1 (CSF1R) neutralising antibody was antifibrotic.These findings suggest differential contributions of alveolar versus interstitial macrophages in RIF, highlighting the fibrogenic role of IMs. The CSF1/CSF1R pathway was identified as a new therapeutic target to inhibit RIF. Copyright ©ERS 2018.

  7. Intracerebral abscess: A complication of severe cystic fibrosis lung disease

    OpenAIRE

    Fenton, Mark E; Cockcroft, Donald W; Gjevre, John A

    2008-01-01

    Intracerebral abscess is an uncommon complication of severe cystic fibrosis lung disease. The present report describes a case of fatal multiple intracerebral abscesses in a patient with a severely bronchiectatic, nonfunctioning right lung and chronic low-grade infection. The patient was previously turned down for pneumonectomy. Intracerebral abscess in cystic fibrosis and the potential role of pneumonectomy in the present patient are discussed.

  8. Automated quantification of renal interstitial fibrosis for computer-aided diagnosis: A comprehensive tissue structure segmentation method.

    Science.gov (United States)

    Tey, Wei Keat; Kuang, Ye Chow; Ooi, Melanie Po-Leen; Khoo, Joon Joon

    2018-03-01

    Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses. This study proposes an automated quantification system for measuring the amount of interstitial fibrosis in renal biopsy images as a consistent basis of comparison among pathologists. The system extracts and segments the renal tissue structures based on colour information and structural assumptions of the tissue structures. The regions in the biopsy representing the interstitial fibrosis are deduced through the elimination of non-interstitial fibrosis structures from the biopsy area and quantified as a percentage of the total area of the biopsy sample. A ground truth image dataset has been manually prepared by consulting an experienced pathologist for the validation of the segmentation algorithms. The results from experiments involving experienced pathologists have demonstrated a good correlation in quantification result between the automated system and the pathologists' visual evaluation. Experiments investigating the variability in pathologists also proved the automated quantification error rate to be on par with the average intra-observer variability in pathologists' quantification. Interstitial fibrosis in renal biopsy samples is a scarring tissue structure that may be visually quantified by pathologists as an indicator to the presence and extent of chronic kidney disease. The standard method of quantification by visual evaluation presents reproducibility issues in the diagnoses due to the uncertainties in human judgement. An automated quantification system for accurately measuring the amount of interstitial fibrosis in renal biopsy images is presented as a consistent basis of comparison among pathologists. The system identifies the renal tissue structures

  9. The classification, natural history and radiological/histological appearance of idiopathic pulmonary fibrosis and the other idiopathic interstitial pneumonias

    Directory of Open Access Journals (Sweden)

    G. Raghu

    2008-12-01

    Full Text Available The idiopathic interstitial pneumonias (IIPs are a heterogeneous group of rare interstitial lung diseases (ILDs or diffuse parenchymal lung diseases, which, as their name implies, are of unknown aetiology. The past 10 yrs have seen important advances in the classification of the IIPs into idiopathic pulmonary fibrosis (IPF and its corresponding histopathological pattern of usual interstitial pneumonia (UIP, plus six non-IPF IIP subtypes. The present article will look at the current classification of IIPs, arising from the Consensus Statement of the American Thoracic Society and European Respiratory Society, and discusses the importance of differential diagnosis of IPF from the non-IPF IIP subtypes, especially nonspecific interstitial pneumonia. Diagnosis of IIPs is a dynamic process involving close collaboration between pulmonologists, radiologists and pathologists. Increasingly accurate diagnosis of IPF has been made possible by the use of high-resolution computed tomography (HRCT and refinements in surgical lung biopsy. In IPF, a lung HRCT will typically reveal irregular reticular opacities, traction bronchiestasis and, most importantly, peripheral honeycombing. In contrast, histological examination shows evidence of UIP manifesting as typically subpleural and paraseptal established fibrosis, often with honeycomb changes, associated with mild chronic inflammation and varying numbers of fibroblastic foci in continuity with the edges of areas of established fibrosis. Despite these advances, obtaining a consistent and uniform diagnosis of idiopathic interstitial pneumonias is difficult, with studies showing significant disagreement in the diagnosis of interstitial lung diseases between academic centres of expertise and community-based clinicians. Greater interaction between academic and community clinicians, together with improved education, is needed to bridge this gap.

  10. Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis

    Directory of Open Access Journals (Sweden)

    Primiani A

    2014-05-01

    Full Text Available Andrea Primiani,1 Dora Dias-Santagata,1 A John Iafrate,1 Richard L Kradin1,2 1Pathology Service, 2Pulmonary Medicine/Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Abstract: Cigarette smoking is an established cause of lung cancer. However, pulmonary fibrosis is also an independent risk factor for the development of lung cancer. Smoking-related interstitial fibrosis (SRIF has recently been reported. We hypothesized that adenocarcinomas in lungs with SRIF might show distinct molecular changes and examined the molecular phenotype of 168 resected lung adenocarcinomas in lungs with and without SRIF. The diagnosis of SRIF was determined by histological examination, based on the presence of alveolar septal thickening, due to pauci-inflamed, hyalinized, “ropy” collagen, in areas of lung greater than 1 cm away from the tumor. Tumors were concomitantly examined genotypically for mutations in genes frequently altered in cancer, including EGFR and KRAS, by SNaPshot and by fluorescence in situ hybridization for possible ALK rearrangements. Fluorescence in situ hybridization for ROS1 rearrangement (n=36 and/or MET amplification (n=31 were performed when no mutation was identified by either SNaPshot or ALK analysis. Sixty-five cases (38.7% showed SRIF, which was distributed in all lobes of the lungs examined. No differences were observed in sex, average age, or smoking history in patients with and without SRIF. There was no difference in either the percent or types of adenocarcinoma genetic mutations in patients with SRIF versus those without. This data suggests that SRIF does not represent an independent risk factor for the development of the major known and targeted mutations seen in pulmonary adenocarcinoma. However, additional research is required to investigate the potential significance of SRIF in the pathogenesis of lung cancer. Keywords: lung, cancer, smoking, SRIF

  11. Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Aggarwal, Rohit; McBurney, Christine; Schneider, Frank; Yousem, Samuel A; Gibson, Kevin F; Lindell, Kathleen; Fuhrman, Carl R; Oddis, Chester V

    2017-03-01

    To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan-Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MA-UIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and event-free survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P < 0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MA-UIP is superior to that of IPF-UIP. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology

  12. EMMPRIN expression is involved in the development of interstitial fibrosis and tubular atrophy in human kidney allografts.

    Science.gov (United States)

    Kemmner, Stephan; Schulte, Christian; von Weyhern, Claus Hann; Schmidt, Roland; Baumann, Marcus; Heemann, Uwe; Renders, Lutz; Schmaderer, Christoph

    2016-03-01

    Matrix metalloproteinases (MMP) are involved in the development of interstitial fibrosis and tubular atrophy (IF/TA) in renal disease. The synthesis of MMP is activated by the extracellular matrix metalloproteinases inducer protein (EMMPRIN). To analyze the role of EMMPRIN in IF/TA, we retrospectively detected EMMPRIN expression in specimens of human renal allografts with various levels of IF/TA. Immunohistochemistry was performed to detect EMMPRIN expression. In a retrospective analysis, a total cohort of 50 specimens were divided according to BANFF-classification into four subgroups (0-3): no, mild (≤ 25%), moderate (26-50%), or severe (>50%) IF/TA. Among other parameters, renal function was analyzed and compared to EMMPRIN expression. In 24 of 38 biopsies, we detected positive EMMPRIN staining. All nephrectomy (n = 12) samples were negative for EMMPRIN. Positive staining in the biopsy samples was detectable on the basolateral side of tubular epithelial cells. EMMPRIN staining was negatively correlated with IF/TA (p EMMPRIN expression in IF/TA groups 0 and 3 (p = 0.021) and groups 1 and 3 (p = 0.004). Furthermore, we found significant correlations between EMMPRIN staining and renal function. Our data suggest that EMMPRIN is involved in the pathophysiology of IF/TA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Treatment and education reduce the severity of schistosomiasis periportal fibrosis

    Directory of Open Access Journals (Sweden)

    Paula Carolina Valenca Silva

    2013-07-01

    Full Text Available Introduction This study evaluates the factors associated with the development of severe periportal fibrosis in patients with Schistosoma mansoni. Methods A cross-sectional study was conducted from April to December 2012 involving 178 patients infected with S. mansoni who were treated in the Hospital das Clínicas of Pernambuco, Brazil. Information regarding risk factors was obtained using a questionnaire. Based on the patients' epidemiological history, clinical examination, and upper abdomen ultrasound evaluation, patients were divided into 2 groups: 137 with evidence of severe periportal fibrosis and 41 patients without fibrosis or with mild or moderate periportal fibrosis. Univariate and multivariate analyses were conducted using EpiInfo software version 3.5.5. Results Illiterate individuals (30.1% and patients who had more frequent contact with contaminated water in towns in the Zona da Mata of Pernambuco (33.2% were at greater risk for severe periportal fibrosis. Based on multivariate analysis, it was determined that an education level of up to 11 years of study and specific prior treatment for schistosomiasis were preventive factors for severe periportal fibrosis. Conclusions The prevailing sites of the severe forms of periportal fibrosis are still within the Zona da Mata of Pernambuco, although there has been an expansion to urban areas and the state coast. Specific treatment and an increased level of education were identified as protective factors, indicating the need for implementing social, sanitary, and health education interventions aimed at schistosomiasis to combat the risk factors for this major public health problem.

  14. Restraint stress intensifies interstitial K+ accumulation during severe hypoxia

    Directory of Open Access Journals (Sweden)

    Christian eSchnell

    2012-03-01

    Full Text Available Chronic stress affects neuronal networks by inducing dendritic retraction, modifying neuronal excitability and plasticity, and modulating glial cells. To elucidate the functional consequences of chronic stress for the hippocampal network, we submitted adult rats to daily restraint stress for three weeks (6 h/day. In acute hippocampal tissue slices of stressed rats, basal synaptic function and short-term plasticity at Schaffer collateral/CA1 neuron synapses were unchanged while long-term potentiation was markedly impaired. The spatiotemporal propagation pattern of hypoxia-induced spreading depression episodes was indistinguishable among control and stress slices. However, the duration of the extracellular direct current (DC potential shift was shortened after stress. Moreover, K+ fluxes early during hypoxia were more intense, and the postsynaptic recoveries of interstitial K+ levels and synaptic function were slower. Morphometric analysis of immunohistochemically stained sections suggested hippocampal shrinkage in stressed rats, and the number of cells that are immunoreactive for GFAP (glial fibrillary acidic protein was increased in the CA1 subfield indicating activation of astrocytes. Western blots showed a marked downregulation of the inwardly rectifying K+ channel Kir4.1 in stressed rats. Yet, resting membrane potentials, input resistance and K+-induced inward currents in CA1 astrocytes were indistinguishable from controls. These data indicate an intensified interstitial K+ accumulation during hypoxia in the hippocampus of chronically stressed rats which seems to arise from a reduced interstitial volume fraction rather than impaired glial K+ buffering. One may speculate that chronic stress aggravates hypoxia-induced pathophysiological processes in the hippocampal network and that this has implications for the ischemic brain.

  15. Plzf as a Candidate Gene Predisposing the Spontaneously Hypertensive Rat to Hypertension, Left Ventricular Hypertrophy, and Interstitial Fibrosis

    Czech Academy of Sciences Publication Activity Database

    Liška, F.; Mancini, M.; Krupková, M.; Chylíková, B.; Křenová, D.; Šeda, O.; Šilhavý, Jan; Mlejnek, Petr; Landa, Vladimír; Zídek, Václav; d´Amati, G.; Pravenec, Michal; Křen, Vladimír

    2014-01-01

    Roč. 27, č. 1 (2014), s. 99-106 ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP301/10/0756; GA ČR(CZ) GAP301/12/0696; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Grant - others:Univerzita Karlova(CZ) PRVOUK-P25/LF1/2 Institutional support: RVO:67985823 Keywords : hypertension * left ventricular hypertrophy * myocardial interstitial fibrosis * spontaneously hypertensive rat * Plzf (promyelocytic leukemia zinc finger) gene Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.852, year: 2014

  16. Comparison of clinicoradiologic manifestation of nonspecific interstitial pneumonia and usual interstitial pneumonia/idiopathic pulmonary fibrosis: A report from NRITLD

    Directory of Open Access Journals (Sweden)

    Tafti Saeid

    2008-01-01

    Full Text Available Background: Ever since Katzenstein and Fiorelli introduced the term nonspecific interstitial pneumonia (NSIP to denote those cases of interstitial pneumonia that cannot be categorized as any of the other types of idiopathic interstitial pneumonias (IIP, there has been continuing debate on whether it is a real clinical entity or not. The American Thoracic Society/European Respiratory Symposium task group tried to identify idiopathic NSIP as a separate disease and exclude it from the category of IIP. However, it appears that the clinical presentation of NSIP and usual interstitial pneumonia (UIP are the same. Objective : To show that the radiologic features of NSIP and UIP should be relied upon, instead of clinical presentation and pathologic findings, to differentiate between the two. Materials and Methods: Consecutive patients who had received a diagnosis of either NSIP or UIP on the basis of open lung biopsy between January 2001 and December 2007 were identified for inclusion in this retrospective review. The study included 61 subjects: 32 men and 29 women with a mean age of 59.39 ± 14.5 years. Chest computed tomography images of all the cases were collected for a review. High resolution computed tomography (HRCT and all pathologic specimens were also evaluated. A weighted kappa coefficient was used to evaluate whether radiology can be used instead of biopsy for the diagnosis of NSIP and UIP. Comparison of the mean ages and the time intervals (i.e., interval between symptom onset and the time of diagnosis in the UIP and NSIP groups was done using the Mann-Whitney U test. Association between gender and biopsy result was evaluated by the Fisher exact test. Data were evaluated using SPSS, v.13. Results : Sixty-one patients were included in this study, 32 were male and 29 were female. On the basis of biopsy findings, 50 (82% patients had UIP and 11 (18% had NSIP. Thirty (60% of the 50 patients who had UIP were male and 20 (40% were female; 2 (18

  17. Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways.

    Science.gov (United States)

    Li, Xuelian; Wang, GuoYuan; QiLi, MuGe; Liang, HaiHai; Li, TianShi; E, XiaoQiang; Feng, Ying; Zhang, Ying; Liu, Xiao; Qian, Ming; Xu, BoZhi; Shen, ZhiHang; Gitau, Samuel Chege; Zhao, DanDan; Shan, HongLi

    2018-01-01

    Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload-induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg-1·day-1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/β-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and β-catenin levels were also significantly inhibited in vivo and in vitro. Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/β-catenin signalling pathways. © 2018 The Author(s). Published by S. Karger AG, Basel.

  18. Anaesthesia for parturients with severe cystic fibrosis: a case series.

    LENUS (Irish Health Repository)

    Deighan, M

    2014-02-01

    Cystic fibrosis affects 1 in 1600-2500 live births and is inherited in an autosomal recessive manner. It primarily involves the respiratory, gastrointestinal and reproductive tracts, with impaired clearance of, and obstruction by, increasingly viscous secretions. Severe respiratory disease, diabetes and gastro-oesophageal reflux may result. Improvements in medical management and survival of cystic fibrosis patients means more are committing to pregnancies. Although guidance for anaesthesia in this patient group is available, management and outcome data associated with more severe cases are sparse. Patients with severe cystic fibrosis require multidisciplinary input and should be managed in a tertiary referral centre. Close monitoring of respiratory function and preoperative optimisation during pregnancy are mandatory. The risk of preterm labour and delivery is increased. Pregnancy and delivery can be managed successfully, even in patients with FEV1 <40% predicted. Neuraxial anaesthesia and analgesia should be the technique of choice for delivery. Postoperative care should be carried out in a critical care setting with the provision of postoperative ventilation if necessary.

  19. Crackle pitch and rate do not vary significantly during a single automated-auscultation session in patients with pneumonia, congestive heart failure, or interstitial pulmonary fibrosis.

    Science.gov (United States)

    Vyshedskiy, Andrey; Ishikawa, Sadamu; Murphy, Raymond L H

    2011-06-01

    To determine the variability of crackle pitch and crackle rate during a single automated-auscultation session with a computerized 16-channel lung-sound analyzer. Forty-nine patients with pneumonia, 52 with congestive heart failure (CHF), and 18 with interstitial pulmonary fibrosis (IPF) performed breathing maneuvers in the following sequence: normal breathing, deep breathing, cough several times; deep breathing, vital-capacity maneuver, and deep breathing. From the auscultation recordings we measured the crackle pitch and crackle rate. Crackle pitch variability, expressed as a percentage of the average crackle pitch, was small in all patients and in all maneuvers: pneumonia 11%, CHF 11%, pulmonary fibrosis 7%. Crackle rate variability was also small: pneumonia 31%, CHF 32%, IPF 24%. Compared to the first deep-breathing maneuver (100%), the average crackle pitch did not significantly change following coughing (pneumonia 100%, CHF 103%, IPF 100%), the vital-capacity maneuver (pneumonia 100%, CHF 92%, IPF 104%), or during quiet breathing (pneumonia 97%, CHF 100%, IPF 104%). Similarly, the average crackle rate did not change significantly following coughing (pneumonia 105%, CHF 110%, IPF 90%) or the vital-capacity maneuver (pneumonia 102%, CHF 101%, IPF 99%). However, during normal breathing the crackle rate was significantly lower in the patients with pneumonia (74%, P auscultation session suggests that crackle rate can be used to follow the course of cardiopulmonary illnesses such as pneumonia, IPF, and CHF.

  20. Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies.

    Science.gov (United States)

    Mariani, Laura H; Martini, Sebastian; Barisoni, Laura; Canetta, Pietro A; Troost, Jonathan P; Hodgin, Jeffrey B; Palmer, Matthew; Rosenberg, Avi Z; Lemley, Kevin V; Chien, Hui-Ping; Zee, Jarcy; Smith, Abigail; Appel, Gerald B; Trachtman, Howard; Hewitt, Stephen M; Kretzler, Matthias; Bagnasco, Serena M

    2018-02-01

    Interstitial fibrosis (IF), tubular atrophy (TA) and interstitial inflammation (II) are known determinants of progression of renal disease. Standardized quantification of these features could add value to current classification of glomerulopathies. We studied 315 participants in the Nephrotic Syndrome Study Network (NEPTUNE) study, including biopsy-proven minimal change disease (MCD = 98), focal segmental glomerulosclerosis (FSGS = 121), membranous nephropathy (MN = 59) and IgA nephropathy (IgAN = 37). Cortical IF, TA and II were quantified (%) on digitized whole-slide biopsy images, by five pathologists with high inter-reader agreement (intra-class correlation coefficient >0.8). Tubulointerstitial messenger RNA expression was measured in a subset of patients. Multivariable Cox proportional hazards models were fit to assess association of IF with the composite of 40% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD) and separately as well, and with complete remission (CR) of proteinuria. IF was highly correlated with TA (P  0.4, false discovery rate (FDR) < 0.01), including upstream regulators such as tumor necrosis factor, interferon gamma (IFN-gamma), and transforming growth factor beta 1 (TGF-B1), and signaling pathways for antigen presentation and hepatic fibrosis. The degree of IF is associated with risk of eGFR decline across different types of proteinuric glomerulopathy, correlates with inflammatory and fibrotic gene expression, and may have predictive value in assessing risk of progression. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  1. T2 relaxation time is related to liver fibrosis severity

    Science.gov (United States)

    Siqueira, Luiz; Uppal, Ritika; Alford, Jamu; Fuchs, Bryan C.; Yamada, Suguru; Tanabe, Kenneth; Chung, Raymond T.; Lauwers, Gregory; Chew, Michael L.; Boland, Giles W.; Sahani, Duhyant V.; Vangel, Mark; Hahn, Peter F.; Caravan, Peter

    2016-01-01

    echo T2 weighted data. Statistical comparison was performed using ANOVA. Results (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4±2.9 ms, n=6 patients); mild (Ishak 1–2) 66.7±1.9 ms (n=30); moderate (Ishak 3–4) 71.6±1.7 ms (n=26); severe (Ishak 5–6) 72.4±1.4 ms (n=61); with relatively low standard error (~2.9 ms). There was a statistically significant difference between degrees of mild (Ishak fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA Pliver (e.g., 20–100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9). Conclusions The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis. PMID:27190762

  2. Smoking-related interstitial fibrosis combined with pulmonary emphysema: computed tomography-pathologic correlative study using lobectomy specimens.

    Science.gov (United States)

    Otani, Hideji; Tanaka, Tomonori; Murata, Kiyoshi; Fukuoka, Junya; Nitta, Norihisa; Nagatani, Yukihiro; Sonoda, Akinaga; Takahashi, Masashi

    2016-01-01

    To evaluate the incidence and pathologic correlation of thin-section computed tomography (TSCT) findings in smoking-related interstitial fibrosis (SRIF) with pulmonary emphysema. Our study included 172 consecutive patients who underwent TSCT and subsequent lobectomy. TSCT findings including clustered cysts with visible walls (CCVW) and ground-glass attenuation with/without reticulation (GGAR) were evaluated and compared in nonsmokers and smokers and among lung locations. TSCT findings, especially CCVW, were also compared with histological findings using lobectomy specimens. The incidence of CCVW and GGAR was significantly higher in smokers than in nonsmokers (34.1% and 40.7%, respectively, vs 2.0% and 12.2%). CCVW and GGAR were frequently found in the lower and peripheral zones. Histologically, CCVW corresponded more often with SRIF with emphysema than usual interstitial pneumonia (UIP, 63.3% vs 30%). CCVW of irregular size and shape were seen in 19 of 20 SRIF with emphysema and in seven of nine UIP-manifested areas with similar round cysts. A less-involved subpleural parenchyma was observed more frequently in SRIF with emphysema. SRIF with emphysema is a more frequent pathological finding than UIP in patients with CCVW on TSCT. The irregular size and shape of CCVW and a less-involved subpleural parenchyma may be a clue suggesting the presence of SRIF with emphysema.

  3. Inhibition mechanism of compound ethanol extracts from wuweizi (fructus schisandrae chinensis) on renal interstitial fibrosis in diabetic nephropathy model mice.

    Science.gov (United States)

    Zhang, Yanqiu; Zhang, Daning; Zhang, Mianzhi

    2012-12-01

    To evaluate inhibition effect and mechanism of compound ethanol extracts from Wuweizi (Fructus Schisandrae Chinensis), Chuanxiong (Rhizoma Chuanxiong) and Muli (Cocha Ostreae) (FRC) on glomerular and tubular interstitial fibrosis in streptozocin (STZ)-induced diabetic nephropathy (ND) model mice. Twenty-seven male C57BL/6 mice were divided randomly into 3 groups: nondibetic (ND), STZ-induced diabetic (D), and STZ-induced diabetic that were treated with 5 g x kg(-1) x day(-1) of FRC by oral gavage (D(FRC)), with 9 in each group. The protein expressions of E-cadherin, alpha-smooth muscle actin (alpha-SMA), Plasminogen Activator Inhibitor-1 (PAL-1) in renal tissues were investigated by Western blotting. The expressions of fibronectin (FN) and alpha-SMA were detected by immunohistochemical method. The morphological changes of renal tissues were observed under a microscope. Renal tissues in the D(FRC) group showed a lessened degree of fibrosis. Meanwhile, the expressions of FN, alpha-SMA and PAI-1 were significantly lower in the D(FRC) group than those in the D group (all P < 0.05). FRC can ameliorate the DN in the C57BL/6 mice, and its mechanism may relate to inhibition on the epithelial to mesenchymal transdifferentiation, endothelial-myofibroblast transition and PAL-1 expression.

  4. Hypersensitivity pneumonia-nonspecific interstitial pneumonia/fibrosis histopathologic presentation: a study in diagnosis and long-term management.

    Science.gov (United States)

    Jacobs, Robert L; Andrews, Charles P

    2003-02-01

    Nonspecific interstitial pneumonia/fibrosis (NSIP) has been classified a form of idiopathic interstitial pneumonia/fibrosis. We have shown that cases of NSIP without demonstrable serum precipitins may be caused by inhalation of high levels of mold and/or bacteria in closed environments. We report a patient with a clinical and histopathologic diagnosis of NSIP without serum precipitins caused by a microbial contamination in her home. Her case was converted from an acute to an insidious clinical presentation by inadequate remediation. A prolonged avoidance-challenge technique demonstrated that this case of NSIP was a form of hypersensitivity pneumonia that was reversible by effective remediation. The patient was identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and a transbronchial lung biopsy. She was further evaluated with a detailed environmental history, serologic tests, and investigation of the home environment. An environmental avoidance and challenge technique was performed to confirm cause and effect and to determine that remediation had been effective. Review of the biopsy showed NSIP and failed to reveal any non-caseating granuloma formation. Investigation of the home revealed a Cladosporium species contamination of the air conditioning system and Penicillium species beneath an entryway carpet. Serum precipitins to commercial antigens of common mold to the south Texas area were negative. Avoidance and challenge techniques confirmed the home as the causative environment in this case of NSIP. The patient has been free of signs and symptoms and has taken no medication for interstitial lung disease over the past 30 months. Some cases of NSIP may be caused by inhalation of microbial antigen(s) in a closed environment. An environmental challenge technique was an effective method to determine the causative environment and confirm that remediation had been effective. Inadequate remediation may lead to symptomatic

  5. Comparison of Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia: Quantification of Disease Severity and Discrimination between Two Diseases on HRCT Using a Texture-Based Automated System

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Ok; Kim, Dong Soon [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Young Kyung [East-West Neo Medical Center of Kyung Hee University, Seoul (Korea, Republic of); Lee, Jeong Jin [The Catholic University of Korea, Seoul (Korea, Republic of)

    2011-06-15

    To evaluate the usefulness of an automated system for quantification and discrimination of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). An automated system to quantify six regional high-resolution CT (HRCT) patterns: normal, NL; ground-glass opacity, GGO; reticular opacity, RO; honeycombing, HC; emphysema, EMPH; and consolidation, CONS, was developed using texture and shape features. Fifty-four patients with pathologically proven UIP (n = 26) and pathologically proven NSIP (n 28) were included as part of this study. Inter-observer agreement in measuring the extent of each HRCT pattern between the system and two thoracic radiologists were assessed in 26 randomly selected subsets using an interclass correlation coefficient (ICC). A linear regression analysis was used to assess the contribution of each disease pattern to the pulmonary function test parameters. The discriminating capacity of the system between UIP and NSIP was evaluated using a binomial logistic regression. The overall ICC showed acceptable agreement among the system and the two radiologists (r = 0.895 for the abnormal lung volume fraction, 0.706 for the fibrosis fraction, 0.895 for NL, 0.625 for GGO, 0.626 for RO, 0.893 for HC, 0.800 for EMPH, and 0.430 for CONS). The volumes of NL, GGO, RO, and EMPH contribute to forced expiratory volume during one second (FEV1) (r = 0.72, {beta} values, 0.84, 0.34, 0.34 and 0.24, respectively) and forced vital capacity (FVC) (r 0.76, {beta} values, 0.82, 0.28, 0.21 and 0.34, respectively). For diffusing capacity (DLco), the volumes of NL and HC were independent contributors in opposite directions (r = 0.65, {beta} values, 0.64, -0.21, respectively). The automated system can help discriminate between UIP and NSIP with an accuracy of 82%. The automated quantification system of regional HRCT patterns can be useful in the assessment of disease severity and may provide reliable agreement with the radiologists' results. In

  6. Comparison of usual interstitial pneumonia and nonspecific interstitial pneumonia: quantification of disease severity and discrimination between two diseases on HRCT using a texture-based automated system.

    Science.gov (United States)

    Park, Sang Ok; Seo, Joon Beom; Kim, Namkug; Lee, Young Kyung; Lee, Jeongjin; Kim, Dong Soon

    2011-01-01

    To evaluate the usefulness of an automated system for quantification and discrimination of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). An automated system to quantify six regional high-resolution CT (HRCT) patterns: normal, NL; ground-glass opacity, GGO; reticular opacity, RO; honeycombing, HC; emphysema, EMPH; and consolidation, CONS, was developed using texture and shape features. Fifty-four patients with pathologically proven UIP (n = 26) and pathologically proven NSIP (n = 28) were included as part of this study. Inter-observer agreement in measuring the extent of each HRCT pattern between the system and two thoracic radiologists were assessed in 26 randomly selected subsets using an interclass correlation coefficient (ICC). A linear regression analysis was used to assess the contribution of each disease pattern to the pulmonary function test parameters. The discriminating capacity of the system between UIP and NSIP was evaluated using a binomial logistic regression. The overall ICC showed acceptable agreement among the system and the two radiologists (r = 0.895 for the abnormal lung volume fraction, 0.706 for the fibrosis fraction, 0.895 for NL, 0.625 for GGO, 0.626 for RO, 0.893 for HC, 0.800 for EMPH, and 0.430 for CONS). The volumes of NL, GGO, RO, and EMPH contribute to forced expiratory volume during one second (FEV₁) (r = 0.72, β values, 0.84, 0.34, 0.34 and 0.24, respectively) and forced vital capacity (FVC) (r = 0.76, β values, 0.82, 0.28, 0.21 and 0.34, respectively). For diffusing capacity (DL(co)), the volumes of NL and HC were independent contributors in opposite directions (r = 0.65, β values, 0.64, -0.21, respectively). The automated system can help discriminate between UIP and NSIP with an accuracy of 82%. The automated quantification system of regional HRCT patterns can be useful in the assessment of disease severity and may provide reliable agreement with the radiologists' results. In addition, this

  7. Interferon gamma peptidomimetic targeted to interstitial myofibroblasts attenuates renal fibrosis after unilateral ureteral obstruction in mice

    NARCIS (Netherlands)

    Poosti, Fariba; Bansal, Ruchi; Yazdani, Saleh; Prakash, Jai; Beljaars, Leonie; van den Born, Jacob; de Borst, Martin H.; van Goor, Harry; Hillebrands, Jan-Luuk; Poelstra, Klaas

    2016-01-01

    Renal fibrosis cannot be adequately treated since anti-fibrotic treatment is lacking. Interferon-gamma is a pro-inflammatory cytokine with anti-fibrotic properties. Clinical use of interferon-gamma is hampered due to inflammation-mediated systemic side effects. We used an interferon-gamma

  8. Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF-α and TGF-β1/ERK1/2 signaling pathways

    Science.gov (United States)

    Zhang, Changyi; Zhou, Guichi; Chen, Yezeng; Liu, Sizheng; Chen, Fen; Xie, Lichun; Wang, Wei; Zhang, Yonggang; Wang, Tianyou; Lai, Xiulan; Ma, Lian

    2018-01-01

    Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord-derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin-induced rat model of DCM. Male Lewis rats (aged 8-weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1×106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle-injected and negative control rats. Myosin injections in rats (vehicle group and experimental group) for 28 days led to severe fibrosis and significant deterioration of cardiac function indicative of DCM. HuMSC treatment reduced fibrosis as determined by Masson's staining of collagen deposits, as well as quantification of molecular markers of myocardial fibrosis such as collagen I/III, profibrotic factors transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and connective tissue growth factor (CTGF). HuMSC treatment restored cardiac function as observed using echocardiography. In addition, western blot analysis indicated that HuMSC injections in DCM rats inhibited the expression of TNF-α, extracellular-signal regulated kinase 1/2 (ERK1/2) and TGF-β1, which is a master switch for inducing myocardial fibrosis. These findings suggested that HuMSC injections attenuated myocardial fibrosis and dysfunction in a rat model of DCM, likely by inhibiting TNF-α and the TGF-β1/ERK1/2 fibrosis pathways. Therefore, HuMSC treatment may represent a potential therapeutic method for treatment of DCM. PMID:29115435

  9. Mesenchymal stem cell-derived inflammatory fibroblasts mediate interstitial fibrosis in the aging heart.

    Science.gov (United States)

    Trial, JoAnn; Entman, Mark L; Cieslik, Katarzyna A

    2016-02-01

    Pathologic fibrosis in the aging mouse heart is associated with dysregulated resident mesenchymal stem cells (MSC) arising from reduced stemness and aberrant differentiation into dysfunctional inflammatory fibroblasts. Fibroblasts derived from aging MSC secrete higher levels of 1) collagen type 1 (Col1) that directly contributes to fibrosis, 2) monocyte chemoattractant protein-1 (MCP-1) that attracts leukocytes from the blood and 3) interleukin-6 (IL-6) that facilitates transition of monocytes into myeloid fibroblasts. The transcriptional activation of these proteins is controlled via the farnesyltransferase (FTase)-Ras-Erk pathway. The intrinsic change in the MSC phenotype acquired by advanced age is specific for the heart since MSC originating from bone wall (BW-MSC) or fibroblasts derived from them were free of these defects. The potential therapeutic interventions other than clinically approved strategies based on findings presented in this review are discussed as well. This article is a part of a Special Issue entitled "Fibrosis and Myocardial Remodeling". Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Peroxiredoxin 5 Protects TGF-β Induced Fibrosis by Inhibiting Stat3 Activation in Rat Kidney Interstitial Fibroblast Cells.

    Directory of Open Access Journals (Sweden)

    Hoon-In Choi

    Full Text Available Renal fibrosis is a common final pathway of end-stage kidney disease which is induced by aberrant accumulation of myofibroblasts. This process is triggered by reactive oxygen species (ROS and proinflammatory cytokines generated by various source of injured kidney cells. Peroxiredoxin 5 (Prdx5 is a thiol-dependent peroxidase that reduces oxidative stress by catalyzing intramolecular disulfide bonds. Along with its antioxidant effects, expression level of Prdx5 also was involved in inflammatory regulation by immune stimuli. However, the physiological effects and the underlying mechanisms of Prdx5 in renal fibrosis have not been fully characterized. Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO for 1 or 7 days. For the in vitro model, NRK49F cells, a rat kidney interstitial fibroblast cell lines, were treated with transforming growth factor β (TGF-β for 0, 1, 3, or 5 days. To access the involvement of its peroxidase activity in TGF-β induced renal fibrosis, wild type Prdx5 (WT and double mutant Prdx5 (DM, converted two active site cysteines at Cys 48 and Cys 152 residue to serine, were transiently expressed in NRK49F cells. The protein expression of Prdx5 was reduced in UUO kidneys. Upregulation of fibrotic markers, such as fibronectin and alpha-smooth muscle actin (α-SMA, declined at 5 days in time point of higher Prdx5 expression in TGF-β treated NRK49F cells. The overexpression of wild type Prdx5 by transient transfection in NRK49F cells attenuated the TGF-β induced upregulation of fibronectin and α-SMA. On the other hand, the transient transfection of double mutant Prdx5 did not prevent the activation of fibrotic markers. Overexpression of Prdx5 also suppressed the TGF-β induced upregulation of Stat3 phosphorylation, while phosphorylation of Smad 2/3 was unchanged. In conclusion, Prdx5 protects TGF-β induced fibrosis in NRK49F cells by modulating Stat3 activation in a peroxidase activity dependent manner.

  11. Alpha8 Integrin (Itga8 Signalling Attenuates Chronic Renal Interstitial Fibrosis by Reducing Fibroblast Activation, Not by Interfering with Regulation of Cell Turnover.

    Directory of Open Access Journals (Sweden)

    Ines Marek

    Full Text Available The α8 integrin (Itga8 chain contributes to the regulation of cell proliferation and apoptosis in renal glomerular cells. In unilateral ureteral obstruction Itga8 is de novo expressed in the tubulointerstitium and a deficiency of Itga8 results in more severe renal fibrosis after unilateral ureteral obstruction. We hypothesized that the increased tubulointerstitial damage after unilateral ureteral obstruction observed in mice deficient for Itga8 is associated with altered tubulointerstitial cell turnover and apoptotic mechanisms resulting from the lack of Itga8 in cells of the tubulointerstitium. Induction of unilateral ureteral obstruction was achieved by ligation of the right ureter in mice lacking Itga8. Unilateral ureteral obstruction increased proliferation and apoptosis rates of tubuloepithelial and interstitial cells, however, no differences were observed in the tubulointerstitium of mice lacking Itga8 and wild type controls regarding fibroblast or proliferating cell numbers as well as markers of endoplasmic reticulum stress and apoptosis after unilateral ureteral obstruction. In contrast, unilateral ureteral obstruction in mice lacking Itga8 led to more pronounced tubulointerstitial cell activation i.e. to the appearance of more phospho-SMAD2/3-positive cells and more α-smooth muscle actin-positive cells in the tubulointerstitium. Furthermore, a more severe macrophage and T-cell infiltration was observed in these animals compared to controls. Thus, Itga8 seems to attenuate tubulointerstitial fibrosis in unilateral ureteral obstruction not via regulation of cell turnover, but via regulation of TGF-β signalling, fibroblast activation and/or immune cell infiltration.

  12. Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy.

    Science.gov (United States)

    Song, Jeong Ah; Park, Hyun-Ju; Yang, Mi-Jin; Jung, Kyung Jin; Yang, Hyo-Seon; Song, Chang-Woo; Lee, Kyuhong

    2014-07-01

    Polyhexamethyleneguanidine phosphate (PHMG-P) has been widely used as a disinfectant because of its strong bactericidal activity and low toxicity. However, in 2011, the Korea Centers for Disease Control and Prevention and the Ministry of Health and Welfare reported that a suspicious outbreak of pulmonary disease might have originated from humidifier disinfectants. The purpose of this study was to assess the toxicity of PHMG-P following direct exposure to the lung. PHMG-P (0.3, 0.9, or 1.5 mg/kg) was instilled into the lungs of mice. The levels of proinflammatory markers and fibrotic markers were quantified in lung tissues and flow cytometry was used to evaluate T cell distribution in the thymus. Administration of PHMG-P induced proinflammatory cytokines elevation and infiltration of immune cells into the lungs. Histopathological analysis revealed a dose-dependent exacerbation of both inflammation and pulmonary fibrosis on day 14. PHMG-P also decreased the total cell number and the CD4(+)/CD8(+) cell ratio in the thymus, with the histopathological examination indicating severe reduction of cortex and medulla. The mRNA levels of biomarkers associated with T cell development also decreased markedly. These findings suggest that exposure of lung tissue to PHMG-P leads to pulmonary inflammation and fibrosis as well as thymic atrophy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

    International Nuclear Information System (INIS)

    Parra, E.R.; Pincelli, M.S.; Teodoro, W.R.; Velosa, A.P.P.; Martins, V.; Rangel, M.P.; Barbas-Filho, J.V.; Capelozzi, V.L.

    2014-01-01

    Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis

  14. Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Parra, E.R.; Pincelli, M.S. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Teodoro, W.R.; Velosa, A.P.P. [Disciplina de Reumatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, V.; Rangel, M.P.; Barbas-Filho, J.V.; Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-06-04

    Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.

  15. GSTA3 Attenuates Renal Interstitial Fibrosis by Inhibiting TGF-Beta-Induced Tubular Epithelial-Mesenchymal Transition and Fibronectin Expression.

    Directory of Open Access Journals (Sweden)

    Yun Xiao

    Full Text Available Tubular epithelial-mesenchymal transition (EMT has been widely accepted as the underlying mechanisms of renal interstitial fibrosis (RIF. The production of reactive oxygen species (ROS plays a vital role in tubular EMT process. The purpose of this study was to investigate the involved molecular mechanisms in TGF-beta-induced EMT and identify the potential role of glutathione S-transferase alpha 3 (GSTA3 in this process. The iTRAQ screening was performed to identify protein alterations of the rats underwent unilateral-ureteral obstruction (UUO. Protein expression of GSTA3 in patients with obstructive nephropathy and UUO rats was detected by immunohistochemistry. Protein and mRNA expression of GSTA3 in UUO rats and NRK-52E cells were determined by Western blot and RT-PCR. siRNA and overexpression plasmid were transfected specifically to assess the role of GSTA3 in RIF. The generation of ROS was measured by dichlorofluorescein fluorescence analysis. GSTA3 protein and mRNA expression was significantly reduced in UUO rats. Immunohistochemical analysis revealed that GSTA3 expression was reduced in renal cortex in UUO rats and patients with obstructive nephropathy. Treating with TGF-β1 down-regulated GSTA3 expression in NRK-52E cells, which have been found to be correlated with the decreased expression in E-cadherin and megalin and increased expression in α-smooth muscle actin. Furthermore, knocking down GSTA3 in NRK-52 cells led to increased production of ROS and tubular EMT, whereas overexpressing GSTA3 ameliorated ROS production and prevented the occurrence of tubular EMT. GSTA3 plays a protective role against tubular EMT in renal fibrosis, suggesting GSTA3 is a potential therapeutic target for RIF.

  16. CT Analysis of the Anterior Mediastinum in Idiopathic Pulmonary Fibrosis and Nonspecific Interstitial Pneumonia

    International Nuclear Information System (INIS)

    Lee, Chang Hyun; Lee, Hyun Ju; Son, Kyu Ri; Chun, Eun Ju; Lim, Kun Young; Goo, Jin Mo; Im, Jung Gi; Heo, Jeong Nam; Song, Jae Woo

    2006-01-01

    We wanted to determine whether the amount and shape of the anterior mediastinal fat in the patients suffering with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was different from those of the normal control group. We selected patients who suffered with UIP (n 26) and NSIP (n = 26) who had undergone CT scans. Twenty-six controls were selected from individuals with normal CT findings and normal pulmonary function tests. All three groups (n = 78) were individually matched for age and gender. The amounts of anterior mediastinal fat, and the retrosternal anteroposterior (AP) and transverse dimensions of the anterior mediastinal fat were compared by one-way analysis of variance and Bonferroni's test. The shapes of the anterior mediastinum were compared using the Chi-square test. Exact logistic regression analysis and polychotomous logistic regression analysis were employed to assess whether the patients with NSIP or UIP had a tendency to show a convex shape of their anterior mediastinal fat. The amount of anterior mediastinal fat was not different among the three groups (p 0.175). For the UIP patients, the retrosternal AP dimension of the anterior mediastinal fat was shorter (p = 0.037) and the transverse dimension of the anterior mediastinal fat was longer (p = 0.001) than those of the normal control group. For the NSIP patients, only the transverse dimension was significantly longer than those of the normal control group (p < 0.001). The convex shape of the anterior mediastinum was predictive of NSIP (OR = 19.7, CI 3.32-∞, p < 0.001) and UIP (OR = 24.42, CI 4.06-∞, p < 0.001). For UIP patients, the retrosternal AP and transverse dimensions are different from those of normal individuals, whereas the amounts of anterior mediastinal fat are similar. UIP and NSIP patients have a tendency to have a convex shape of their anterior mediastinal fat

  17. CT Analysis of the Anterior Mediastinum in Idiopathic Pulmonary Fibrosis and Nonspecific Interstitial Pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Hyun; Lee, Hyun Ju; Son, Kyu Ri; Chun, Eun Ju; Lim, Kun Young; Goo, Jin Mo; Im, Jung Gi [Seoul National University College of Medicine, Seoul (Korea, Republic of); Heo, Jeong Nam; Song, Jae Woo [University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2006-09-15

    We wanted to determine whether the amount and shape of the anterior mediastinal fat in the patients suffering with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was different from those of the normal control group. We selected patients who suffered with UIP (n 26) and NSIP (n = 26) who had undergone CT scans. Twenty-six controls were selected from individuals with normal CT findings and normal pulmonary function tests. All three groups (n = 78) were individually matched for age and gender. The amounts of anterior mediastinal fat, and the retrosternal anteroposterior (AP) and transverse dimensions of the anterior mediastinal fat were compared by one-way analysis of variance and Bonferroni's test. The shapes of the anterior mediastinum were compared using the Chi-square test. Exact logistic regression analysis and polychotomous logistic regression analysis were employed to assess whether the patients with NSIP or UIP had a tendency to show a convex shape of their anterior mediastinal fat. The amount of anterior mediastinal fat was not different among the three groups (p 0.175). For the UIP patients, the retrosternal AP dimension of the anterior mediastinal fat was shorter (p = 0.037) and the transverse dimension of the anterior mediastinal fat was longer (p = 0.001) than those of the normal control group. For the NSIP patients, only the transverse dimension was significantly longer than those of the normal control group (p < 0.001). The convex shape of the anterior mediastinum was predictive of NSIP (OR = 19.7, CI 3.32-{infinity}, p < 0.001) and UIP (OR = 24.42, CI 4.06-{infinity}, p < 0.001). For UIP patients, the retrosternal AP and transverse dimensions are different from those of normal individuals, whereas the amounts of anterior mediastinal fat are similar. UIP and NSIP patients have a tendency to have a convex shape of their anterior mediastinal fat.

  18. Clinical features of usual interstitial pneumonia with anti-neutrophil cytoplasmic antibody in comparison with idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Hosoda, Chiaki; Baba, Tomohisa; Hagiwara, Eri; Ito, Hiroyuki; Matsuo, Norikazu; Kitamura, Hideya; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Ogura, Takashi

    2016-07-01

    Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is occasionally positive in patients with usual interstitial pneumonia (UIP). However, the differences from idiopathic pulmonary fibrosis (IPF/UIP) have not been well documented. We aimed to clarify the clinical, radiological and pathological features of UIP associated with MPO-ANCA (ANCA/UIP). We retrospectively reviewed the medical records of 12 consecutive ANCA/UIP patients not manifesting microscopic polyangiitis and 108 IPF/UIP patients with no autoantibodies, both diagnosed by surgical lung biopsy. There was no significant difference in clinical background, laboratory results and pulmonary function tests between ANCA/UIP patients and IPF/UIP patients except for the percentage of bronchoalveolar lavage neutrophils. HRCT showed subpleural reticulation in both groups. Increased attenuation around honeycombing and cysts was significantly observed in ANCA/UIP. Pathologically, ANCA/UIP had more prominent inflammatory cell infiltration, lymphoid follicles with germinal centres and cellular bronchiolitis. During the disease course, three of 12 patients (25%) developed microscopic polyangiitis. Immunosuppressive treatment tended to be more effective in ANCA/UIP patients, and the survival time in ANCA/UIP patients tended to be longer than those with IPF/UIP. ANCA/UIP may be distinguishable from IPF/UIP with a combination of HRCT findings of increased attenuation around honeycombing and cysts and some of the characteristic pathological findings. In contrast to IPF/UIP, immunosuppressive treatment could be a therapeutic option for ANCA/UIP. © 2016 Asian Pacific Society of Respirology.

  19. Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

    Science.gov (United States)

    Sokai, Akihiko; Handa, Tomohiro; Chen, Fengshi; Tanizawa, Kiminobu; Aoyama, Akihiro; Kubo, Takeshi; Ikezoe, Kohei; Nakatsuka, Yoshinari; Oguma, Tsuyoshi; Hirai, Toyohiro; Nagai, Sonoko; Chin, Kazuo; Date, Hiroshi; Mishima, Michiaki

    2016-04-01

    Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Severe idiopathic pulmonary fibrosis: what can be done?

    Directory of Open Access Journals (Sweden)

    Antonella Caminati

    2017-09-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with mild-to-moderate IPF. This means that early diagnosis is mandatory, because there are no proven effective therapies for severe IPF. This lack of proven therapies may be at least partially due to the fact that severe IPF patients are usually not enrolled in randomised, prospective, multicentre, international trials. Clinical observation experiences and preliminary results of long-term, open-label extensions of clinical trials suggest that both pirfenidone and nintedanib may also slow or decrease progression in patients with severe IPF. However, data are sparse and obtained from a relatively small number of patients. Lung transplantation should be taken into account early and discussed with patients, when indicated. Rehabilitative strategies are important and effective supportive therapies. The needs of patients with severe IPF are similar to those of patients with an advanced neoplastic disease. Palliative care and psychological support play an important role in the relief of symptoms of anxiety and depression. Accordingly, these therapeutic approaches should start early in IPF patients.

  1. Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy.

    Science.gov (United States)

    Li, Ao; Zhang, Xiaoxun; Shu, Mao; Wu, Mingjun; Wang, Jun; Zhang, Jingyao; Wang, Rui; Li, Peng; Wang, Yitao

    2017-07-01

    Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF. The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats. Rats were subjected to UUO and then administered with vehicle, ATG (1 and 3mg/kg/d), or losartan (20mg/kg/d) for 11 consecutive days. The renoprotective effects of ATG were evaluated by histological examination and multiple biochemical assays. Our results suggest that ATG significantly protected the kidney from injury by reducing tubular dilatation, epithelial atrophy, collagen deposition, and tubulointerstitial compartment expansion. ATG administration dramatically decreased macrophage (CD68-positive cell) infiltration. Meanwhile, ATG down-regulated the mRNA levels of pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) and cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ), in the obstructed kidneys. This was associated with decreased activation of nuclear factor κB (NF-κB). ATG attenuated UUO-induced oxidative stress by increasing the activity of renal manganese superoxide dismutase (SOD2), leading to reduced levels of lipid peroxidation. Furthermore, ATG inhibited the epithelial-mesenchymal transition (EMT) of renal tubules by reducing the abundance of transforming growth factor-β1 (TGF-β1) and its type I receptor, suppressing Smad2/3 phosphorylation and nuclear translocation, and up-regulating Smad7 expression. Notably, the efficacy of ATG in renal protection was comparable or even superior to losartan. ATG could protect the kidney from UUO-induced injury and fibrogenesis by suppressing inflammation, oxidative

  2. Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Supanat Worawichawong

    2016-12-01

    Full Text Available Background/Aims: The degree of tubular atrophy and interstitial fibrosis (IFTA is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1 and protective cytokines such as epidermal growth factor (EGF likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN. Methods: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy. MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. Results: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58. By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85, but the improvement over EGF alone was not significant. Conclusion: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.

  3. Interstitial deletion of 5q33.3q35.1 in a boy with severe mental retardation

    OpenAIRE

    Lee, Jin Hwan; Kim, Hyo Jeong; Yoon, Jung Min; Cheon, Eun Jung; Lim, Jae Woo; Ko, Kyong Og; Lee, Gyung Min

    2016-01-01

    Constitutional interstitial deletions of the long arm of chromosome 5 (5q) are quite rare, and the corresponding phenotype is not yet clearly delineated. Severe mental retardation has been described in most patients who present 5q deletions. Specifically, the interstitial deletion of chromosome 5q33.3q35.1, an extremely rare chromosomal aberration, is characterized by mental retardation, developmental delay, and facial dysmorphism. Although the severity of mental retardation varies across cas...

  4. Familial Pulmonary Fibrosis

    Science.gov (United States)

    ... Education & Training Home Conditions Familial Pulmonary Fibrosis Familial Pulmonary Fibrosis Make an Appointment Find a Doctor Ask a ... more members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial ...

  5. Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Alberto Daniel Rocha-Muñoz

    2015-01-01

    Full Text Available Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2 are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD. Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT were compared with 42 RA without lung involvement (RA only. Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P<0.001. In the logistic regression analysis after adjustment for age, disease duration (DD, smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P=0.003 and + RF (P=0.002. In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P=0.02 and with fibrosis score DD (P=0.01, anti-CCP2 titers (P<0.001, and MTX treatment duration (P<0.001. Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.

  6. Risk of acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer in patients with idiopathic pulmonary fibrosis based on preoperative high-resolution computed tomography

    International Nuclear Information System (INIS)

    Suzuki, Hidemi; Sekine, Yasuo; Yoshida, Shigetoshi

    2011-01-01

    In patients with lung cancer accompanied by idiopathic pulmonary fibrosis (IPF), acute exacerbation of the IPF often occurs after pulmonary resection; however, few studies have been done to identify its preexisting risk factors. We analyzed the high-resolution computed tomography (HRCT) findings of IPF to identify the radiological characteristics of IPF susceptible to acute exacerbation after lung cancer surgery. We reviewed retrospectively 28 lung cancer patients with IPF who underwent pulmonary resection. Clinical data, respiratory function, HRCT findings, and historical features were compared between the acute exacerbation (n=9) and nonexacerbation (n=19) groups. The classification of radiological findings of IPF on HRCT was done using a scoring system of seven factors related to the interstitial shadow, including fibrosis, ground-glass opacity, and low-attenuation area. There were no significant differences in clinical background, respiratory function, composite physiologic index, or pathological features between the groups; however, the degree of fibrosis on preoperative HRCT was significantly higher in the exacerbation group (P<0.003). The fibrosis score was higher on the opposite side to the lung cancer in the exacerbation group (P<0.05). Although it is difficult to predict postoperative acute IPF exacerbation, the degree and laterality of co-existing fibrosis seem to be predictors. (author)

  7. A stepwise composite echocardiographic score predicts severe pulmonary hypertension in patients with interstitial lung disease.

    Science.gov (United States)

    Bax, Simon; Bredy, Charlene; Kempny, Aleksander; Dimopoulos, Konstantinos; Devaraj, Anand; Walsh, Simon; Jacob, Joseph; Nair, Arjun; Kokosi, Maria; Keir, Gregory; Kouranos, Vasileios; George, Peter M; McCabe, Colm; Wilde, Michael; Wells, Athol; Li, Wei; Wort, Stephen John; Price, Laura C

    2018-04-01

    European Respiratory Society (ERS) guidelines recommend the assessment of patients with interstitial lung disease (ILD) and severe pulmonary hypertension (PH), as defined by a mean pulmonary artery pressure (mPAP) ≥35 mmHg at right heart catheterisation (RHC). We developed and validated a stepwise echocardiographic score to detect severe PH using the tricuspid regurgitant velocity and right atrial pressure (right ventricular systolic pressure (RVSP)) and additional echocardiographic signs. Consecutive ILD patients with suspected PH underwent RHC between 2005 and 2015. Receiver operating curve analysis tested the ability of components of the score to predict mPAP ≥35 mmHg, and a score devised using a stepwise approach. The score was tested in a contemporaneous validation cohort. The score used "additional PH signs" where RVSP was unavailable, using a bootstrapping technique. Within the derivation cohort (n=210), a score ≥7 predicted severe PH with 89% sensitivity, 71% specificity, positive predictive value 68% and negative predictive value 90%, with similar performance in the validation cohort (n=61) (area under the curve (AUC) 84.8% versus 83.1%, p=0.8). Although RVSP could be estimated in 92% of studies, reducing this to 60% maintained a fair accuracy (AUC 74.4%). This simple stepwise echocardiographic PH score can predict severe PH in patients with ILD.

  8. Imaging focal and interstitial fibrosis with cardiovascular magnetic resonance in athletes with left ventricular hypertrophy: implications for sporting participation.

    LENUS (Irish Health Repository)

    Waterhouse, Deirdre F

    2012-11-01

    Long-term high-intensity physical activity is associated with morphological changes, termed as the \\'athlete\\'s heart\\'. The differentiation of physiological cardiac adaptive changes in response to high-level exercise from pathological changes consistent with an inherited cardiomyopathy is imperative. Cardiovascular magnetic resonance (CMR) imaging allows definition of abnormal processes occurring at the tissue level, including, importantly, myocardial fibrosis. It is therefore vital in accurately making this differentiation. In this review, we will review the role of CMR imaging of fibrosis, and detail CMR characterisation of myocardial fibrosis in various cardiomyopathies, and the implications of fibrosis. Additionally, we will outline advances in imaging fibrosis, in particular T1 mapping. Finally we will address the role of CMR in pre-participation screening.

  9. The Effects of Diabetes Induction on the Rat Heart: Differences in Oxidative Stress, Inflammatory Cells, and Fibrosis between Subendocardial and Interstitial Myocardial Areas

    Directory of Open Access Journals (Sweden)

    Maria C. Guido

    2017-01-01

    Full Text Available Diabetic cardiomyopathy (DCM is characterized by cardiac remodeling and impaired diastolic function that may lead to heart failure. The aim of this study was to evaluate oxidative stress, inflammatory cells, and fibrosis in both subendocardial (SEN and interstitial (INT areas of the myocardium. Male Wistar rats were allocated to 2 groups of 9 animals, a control (CT group and streptozotocin-induced diabetes (DM. After 8 weeks, echocardiography morphometry, protein expression, and confocal microscopy in SEN and INT areas of the left ventricle (LV were performed. The echocardiographic analysis showed that diabetes induction leads to cardiac dilation, hypertrophy, and LV diastolic dysfunction. As compared to CT, the induction of diabetes increased inflammatory cells and fibrosis in both SEN and INT areas of DM myocardium and increased ROS generation only in SEN. Comparing the SEN and INT areas in the DM group, inflammatory cells and fibrosis in SEN were greater than in INT. In conclusion, diabetic myocardium SEN area, wherein oxidative stress was more pronounced, is more susceptible to cardiac dysfunction than INT area. This finding can be important for the understanding of the heart remodeling process occurring in DCM and perhaps to engender targeted therapies to attenuate or revert DCM-related diastolic dysfunction.

  10. Pulmonary Artery Size in Interstitial Lung Disease and Pulmonary Hypertension: Association with Interstitial Lung Disease Severity and Diagnostic Utility

    Directory of Open Access Journals (Sweden)

    Matthew Chin

    2018-06-01

    Full Text Available PurposeIt is postulated that ILD causes PA dilatation independent of the presence of pulmonary hypertension (PH, so the use of PA size to screen for PH is not recommended. The aims of this study were to investigate the association of PA size with the presence and severity of ILD and to assess the diagnostic accuracy of PA size for detecting PH.MethodsIncident patients referred to a tertiary PH centre underwent baseline thoracic CT, MRI and right heart catheterisation (RHC. Pulmonary artery diameter was measured on CT pulmonary angiography and pulmonary arterial areas on MRI. A thoracic radiologist scored the severity of ILD on CT from 0 to 4, 0 = absent, 1 = 1–25%, 2 = 26–50%, 3 = 51–75%, and 4 = 76–100% extent of involvement. Receiver operating characteristic analysis and linear regression were employed to assess diagnostic accuracy and independent associations of PA size.Results110 had suspected PH due to ILD (age 65 years (SD 13, M:F 37:73 and 379 had suspected PH without ILD (age 64 years (SD 13, M:F 161:218. CT derived main PA diameter was accurate for detection of PH in patients both with and without ILD - AUC 0.873, p =< 0.001, and AUC 0.835, p =< 0.001, respectively, as was MRI diastolic PA area, AUC 0.897, p =< 0.001, and AUC 0.857, p =< 0.001, respectively Significant correlations were identified between mean pulmonary arterial pressure (mPAP and PA diameter in ILD (r = 0.608, p < 0.001, and non-ILD cohort (r = 0.426, p < 0.001. PA size was independently associated with mPAP (p < 0.001 and BSA (p = 0.001, but not with forced vital capacity % predicted (p = 0.597, Transfer factor of the lungs for carbon monoxide (TLCO % predicted (p = 0.321 or the presence of ILD on CT (p = 0.905. The severity of ILD was not associated with pulmonary artery dilatation (r = 0.071, p = 0.459.ConclusionsPulmonary arterial pressure elevation leads to pulmonary arterial dilation, which is not independently influenced by the presence or severity of

  11. Increased mortality by septicemia, interstitial pneumonitis and pulmonary fibrosis among bone marrow transplant recipients receiving an increased mean dose rate of total irradiation

    International Nuclear Information System (INIS)

    Ringden, O.; Baaryd, I.; Johansson, B.

    1983-01-01

    Seven bone marrow transplant recipients with acute lymphoblastic leukemia receiving a mean dose rate of 0.07 Gy/min of total body irradiation towards the pelvic midpoint and the lungs had an increased (p<0.01) overall death rate of 86 per cent compared with 33 per cent among 27 patients with acute non-lymphoblastic leukemia or acute lymphoblastic leukemia treated with a mean dose rate of 0.04 Gy/min. Among the patients receiving the higher dose rate there was an increased mortality in causes related to radiation toxicity like early septicemia, interstitial pneumonitis and pulmonary fibrosis, compared with all patients receiving the lower dose rate (p<0.01) and also with 10 patients from this group with acute lymphoblastic leukemia (p<0.02). (Auth.)

  12. ECG strain pattern in hypertension is associated with myocardial cellular expansion and diffuse interstitial fibrosis: a multi-parametric cardiac magnetic resonance study.

    Science.gov (United States)

    Rodrigues, Jonathan C L; Amadu, Antonio Matteo; Ghosh Dastidar, Amardeep; McIntyre, Bethannie; Szantho, Gergley V; Lyen, Stephen; Godsave, Cattleya; Ratcliffe, Laura E K; Burchell, Amy E; Hart, Emma C; Hamilton, Mark C K; Nightingale, Angus K; Paton, Julian F R; Manghat, Nathan E; Bucciarelli-Ducci, Chiara

    2017-04-01

    In hypertension, the presence of left ventricular (LV) strain pattern on 12-lead electrocardiogram (ECG) carries adverse cardiovascular prognosis. The underlying mechanisms are poorly understood. We investigated whether hypertensive ECG strain is associated with myocardial interstitial fibrosis and impaired myocardial strain, assessed by multi-parametric cardiac magnetic resonance (CMR). A total of 100 hypertensive patients [50 ± 14 years, male: 58%, office systolic blood pressure (SBP): 170 ± 30 mmHg, office diastolic blood pressure (DBP): 97 ± 14 mmHg) underwent ECG and 1.5T CMR and were compared with 25 normotensive controls (46 ± 14 years, 60% male, SBP: 124 ± 8 mmHg, DBP: 76 ± 7 mmHg). Native T1 and extracellular volume fraction (ECV) were calculated with the modified look-locker inversion-recovery sequence. Myocardial strain values were estimated with voxel-tracking software. ECG strain (n = 20) was associated with significantly higher indexed LV mass (LVM) (119 ± 32 vs. 80 ± 17 g/m2, P ECG strain (n = 80). ECG strain subjects had significantly impaired circumferential strain compared with hypertensive subjects without ECG strain and controls (-15.2 ± 4.7 vs. -17.0 ± 3.3 vs. -17.3 ± 2.4%, P ECG strain subjects to hypertensive subjects with elevated LVM but no ECG strain, a significantly higher ECV (30 ± 4 vs. 28 ± 3%, P ECG strain in multivariate logistic regression analysis [odds ratio (95th confidence interval): 1.07 (1.02-1.12), P ECG strain is a marker of advanced LVH associated with increased interstitial fibrosis and associated with significant myocardial circumferential strain impairment. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  13. The study on serum and urine of renal interstitial fibrosis rats induced by unilateral ureteral obstruction based on metabonomics and network analysis methods.

    Science.gov (United States)

    Xiang, Zheng; Sun, Hao; Cai, Xiaojun; Chen, Dahui

    2016-04-01

    Transmission of biological information is a biochemical process of multistep cascade from genes/proteins to metabolites. However, because most metabolites reflect the terminal information of the biochemical process, it is difficult to describe the transmission process of disease information in terms of the metabolomics strategy. In this paper, by incorporating network and metabolomics methods, an integrated approach was proposed to systematically investigate and explain the molecular mechanism of renal interstitial fibrosis. Through analysis of the network, the cascade transmission process of disease information starting from genes/proteins to metabolites was putatively identified and uncovered. The results indicated that renal fibrosis was involved in metabolic pathways of glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, riboflavin metabolism, tyrosine metabolism, and sphingolipid metabolism. These pathways involve kidney disease genes such as TGF-β1 and P2RX7. Our results showed that combining metabolomics and network analysis can provide new strategies and ideas for the interpretation of pathogenesis of disease with full consideration of "gene-protein-metabolite."

  14. Combined Pulmonary Fibrosis and Emphysema Syndrome: A New Phenotype within the Spectrum of Smoking-Related Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Karina Portillo

    2012-01-01

    Full Text Available Combined pulmonary fibrosis and emphysema (CPFE is a recently defined syndrome, in which centrilobular and/or paraseptal emphysemas in upper lung zones coexist with pulmonary fibrosis in lower lobes in individuals. These patients have a characteristic lung function profile, with unexpected subnormal dynamic and static lung volumes, contrasting with a significant reduction of carbon monoxide transfer (DLco and exercise hypoxemia. Pulmonary hypertension is highly prevalent in CPFE and is the leading determinant of death. Tobacco smoking has been proposed as the main factor in its etiology, though the pathophysiology and its natural history remain to be determined. High-resolution computed axial tomography is the mandatory tool to confirm the diagnosis. Currently, there is no consensus about its treatment since those published to date on this issue are limited to well-characterised series of cases; hence, a better understanding of this entity may help in the development of future therapeutic approaches.

  15. Reproductive status is associated with the severity of fibrosis in women with hepatitis C.

    Directory of Open Access Journals (Sweden)

    Erica Villa

    Full Text Available Chronic hepatitis C is the main cause of death in patients with end-stage liver disease. Prognosis depends on the increase of fibrosis, whose progression is twice as rapid in men as in women. Aim of the study was to evaluate the effects of reproductive stage on fibrosis severity in women and to compare these findings with age-matched men.A retrospective study of 710 consecutive patients with biopsy-proven chronic hepatitis C was conducted, using data from a clinical database of two tertiary Italian care centers. Four age-matched groups of men served as controls. Data about demographics, biochemistry, liver biopsy and ultrasonography were analyzed. Contributing factors were assessed by multivariate logistic regression analysis.Liver fibrosis was more advanced in the early menopausal than in the fully reproductive (P<0.0001 or premenopausal (P = 0.042 group. Late menopausal women had higher liver fibrosis compared with the other groups (fully reproductive, P<0.0001; premenopausal, P = <0.0001; early menopausal, P = 0.052. Multivariate analyses showed that male sex was independently associated with more severe fibrosis in the groups corresponding to premenopausal (P = 0.048 and early menopausal (P = 0.004 but not late menopausal pairs. In women, estradiol/testosterone ratio decreased markedly in early (vs. reproductive age: P = 0.002 and vs. premenopausal: P<0.0001 and late menopause (vs. reproductive age: P = 0.001; vs. premenopausal: P<0.0001. In men age-matched with menopausal women, estradiol/testosterone ratio instead increased (reproductive age group vs. early: P = 0.002 and vs. late M: P = 0.001.The severity of fibrosis in women worsens in parallel with increasing estrogen deprivation and estradiol/testosterone ratio decrease. Our data provide evidence why fibrosis progression is discontinuous in women and more linear and severe in men, in whom aging-associated estradiol/testosterone ratio increase occurs too late to noticeably influence the

  16. Is sweat chloride predictive of severity of cystic fibrosis lung disease assessed by chest computed tomography?

    NARCIS (Netherlands)

    Caudri, Daan; Zitter, David; Bronsveld, Inez; Tiddens, Harm

    BACKGROUND: Cystic Fibrosis (CF) lung disease is characterized by a marked heterogeneity. Sweat chloride-level is a functional marker of the CF Transmembrane Regulator (CFTR) protein and could be an important predictor of later disease severity. METHODS: In this retrospective analysis children from

  17. Effect of mixing scanner types and reconstruction kernels on the characterization of lung parenchymal pathologies: emphysema, interstitial pulmonary fibrosis and normal non-smokers

    Science.gov (United States)

    Xu, Ye; van Beek, Edwin J.; McLennan, Geoffrey; Guo, Junfeng; Sonka, Milan; Hoffman, Eric

    2006-03-01

    In this study we utilize our texture characterization software (3-D AMFM) to characterize interstitial lung diseases (including emphysema) based on MDCT generated volumetric data using 3-dimensional texture features. We have sought to test whether the scanner and reconstruction filter (kernel) type affect the classification of lung diseases using the 3-D AMFM. We collected MDCT images in three subject groups: emphysema (n=9), interstitial pulmonary fibrosis (IPF) (n=10), and normal non-smokers (n=9). In each group, images were scanned either on a Siemens Sensation 16 or 64-slice scanner, (B50f or B30 recon. kernel) or a Philips 4-slice scanner (B recon. kernel). A total of 1516 volumes of interest (VOIs; 21x21 pixels in plane) were marked by two chest imaging experts using the Iowa Pulmonary Analysis Software Suite (PASS). We calculated 24 volumetric features. Bayesian methods were used for classification. Images from different scanners/kernels were combined in all possible combinations to test how robust the tissue classification was relative to the differences in image characteristics. We used 10-fold cross validation for testing the result. Sensitivity, specificity and accuracy were calculated. One-way Analysis of Variances (ANOVA) was used to compare the classification result between the various combinations of scanner and reconstruction kernel types. This study yielded a sensitivity of 94%, 91%, 97%, and 93% for emphysema, ground-glass, honeycombing, and normal non-smoker patterns respectively using a mixture of all three subject groups. The specificity for these characterizations was 97%, 99%, 99%, and 98%, respectively. The F test result of ANOVA shows there is no significant difference (p <0.05) between different combinations of data with respect to scanner and convolution kernel type. Since different MDCT and reconstruction kernel types did not show significant differences in regards to the classification result, this study suggests that the 3-D AMFM can

  18. Short-term Automated Quantification of Radiologic Changes in the Characterization of Idiopathic Pulmonary Fibrosis Versus Nonspecific Interstitial Pneumonia and Prediction of Long-term Survival.

    Science.gov (United States)

    De Giacomi, Federica; Raghunath, Sushravya; Karwoski, Ronald; Bartholmai, Brian J; Moua, Teng

    2018-03-01

    Fibrotic interstitial lung diseases presenting with nonspecific and overlapping radiologic findings may be difficult to diagnose without surgical biopsy. We hypothesized that baseline quantifiable radiologic features and their short-term interval change may be predictive of underlying histologic diagnosis as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting without honeycombing versus nonspecific interstitial pneumonia (NSIP). Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients with available high-resolution chest computed tomography 4 to 24 months apart were studied. CALIPER software was used for the automated characterization and quantification of radiologic findings. IPF subjects were older (66 vs. 48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval period, compared with NSIP, IPF patients experienced greater functional decline (forced vital capacity, -6.3% vs. -1.7%; P=0.02) and radiologic progression, as noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and decrease in normal (-220 vs. -37.7 mL; P=0.045) and total lung volumes (-198 vs. 58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at baseline, and greater interval decrease in normal lung volumes were predictive of IPF. Both baseline and short-term changes in quantitative radiologic findings were predictive of mortality. Baseline quantitative radiologic findings and assessment of short-term disease progression may help characterize underlying IPF versus NSIP in those with difficult to differentiate clinicoradiologic presentations. Our study supports the possible utility of assessing serial quantifiable high-resolution chest computed tomographic findings for disease differentiation in these 2 entities.

  19. Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis

    Directory of Open Access Journals (Sweden)

    Harsh Shah

    2015-01-01

    Full Text Available We report a case of acute promyelocytic leukemia (APL presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA- containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

  20. Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis.

    Science.gov (United States)

    Shah, Harsh; Bradford, Carol; Sayar, Hamid

    2015-01-01

    We report a case of acute promyelocytic leukemia (APL) presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA-) containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

  1. Severe respiratory failure as a presenting feature of an interstitial lung disease associated with anti-synthetase syndrome (ASS).

    Science.gov (United States)

    Piroddi, Ines Maria Grazia; Ferraioli, Gianluca; Barlascini, Cornelius; Castagneto, Corrado; Nicolini, Antonello

    2016-07-01

    Anti-synthetase syndrome (ASS) is defined as a heterogeneous connective tissue disorder characterized by the association of an interstitial lung disease (ILD) with or without inflammatory myositis with the presence of anti-aminoacyl-tRNA-synthetase antibodies. ILD is one of the major extra-muscular manifestations of polymyositis and dermatomyositis. We report a case of a patient with dyspnea, cough, and intermittent fever as well as ILD associated ASS in the absence of muscular involvement. This patient was admitted to the emergency department with severe respiratory failure requiring non-invasive ventilation. Our patient's case demonstrates that the diagnosis of ASS may not be obvious. However, its diagnosis leads to appropriate and potentially life-saving treatment. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  2. Idiopathic pulmonary fibrosis.

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

    2017-02-23

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

  3. Validation of the interstitial fibrosis and tubular atrophy on the new pathological classification in patients with diabetic nephropathy: A single-center study in China.

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    Zhu, Xuejing; Xiong, Xiaofen; Yuan, Shuguang; Xiao, Li; Fu, Xiao; Yang, Yuan; Tang, Chengyuan; He, Liyu; Liu, Fuyou; Sun, Lin

    2016-04-01

    The association between interstitial fibrosis and tubular atrophy (IFTA) and the clinical outcomes in diabetic nephropathy (DN) remains unclear. This study is to evaluate the clinical predictors and renal prognosis of IFTA score in patients with DN. 52 cases with DN with renal biopsy were divided into three groups according to IFTA score. The χ2 test or Fisher's exact test, Mann-Whitney U-test, Kruskal-Wallis H-test and Spearman's correlation analysis were used in this subject. Ordinal regression mode was utilized to evaluate which clinical factors might be the predictors of IFTA score. Compared to IFTA score 1 group, the patients in score 3 were younger and have greatly lower level of eGFR and hemoglobin and higher serum creatinine (p<0.01). A close relationship between the clinical findings and IFTA was observed, such as IFTA with eGFR(r=-0.58, P<0.01), triglyceride(r=-0.29, P=0.04), Hb (r=-0.38, P<0.01), systolic blood pressure (r=0.29, P=0.04) and urinary protein level (r=0.46, P<0.01); in addition, eGFR (OR 0.31 (95%Cl -1.883 to -0.485) p=0.001) showed statistical significance with IFTA. The 5-year renal survival rate was estimated as 100% in IFTA score 0, 88.9% in score 1, 76.9% in score 2, and 20.0% in score 3. Furthermore, greatly lower level of eGFR, and higher serum creatinine and BUN in the glomerular class IV were seen (p<0.01 vs class II), with positive correlation with IFTA (r=0.51, P<0.01). The renal pathologic diagnosis in IFTA score was a good predictor for renal prognosis in type II DM. eGFR might be a predictor of IFTA in patients with DN. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Breath Alkane as an index of severity for oral submucous fibrosis: A new perspective?

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    Arakeri, Gururaj; Boraks, George; Aljabab, Abdulsalam S; Patil, Shekar Gowda; Merkx, M A W; Brennan, Peter A

    2017-01-01

    Oral submucous fibrosis (OSMF) is a devastating disease commonly seen in the Asian subcontinent that results in significant functional morbidity for patients and has a high potential for malignant transformation. Over the last three decades, different diagnostic methods have been described to quantify and grade OSMF severity. Some methods have been used with perceived favorable outcomes although recurrence and malignant transformation remains a problem in many cases, and OSMF presents a major therapeutic challenge. We present a simple, noninvasive and less time-consuming diagnostic method which measures the severity of OSMF, helping to predict its malignant transformation and monitoring the effect of medical therapy on this disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

    2003-09-01

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

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

    Science.gov (United States)

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

    2015-07-01

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

  7. An Interstitial Deletion at 7q33-36.1 in a Patient with Intellectual Disability, Significant Language Delay, and Severe Microcephaly

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    Trupti Kale

    2016-01-01

    Full Text Available Interstitial deletions of the distal 7q region are considered a rare entity. In this report, we describe a seven-year-old male with a heterozygous interstitial deletion at 7q33-36.1 with characteristic dysmorphic facial features, intellectual disability, severe microcephaly, and significant language delay. The primary focus of our report is to compare our case with the few others in the literature describing interstitial deletions at the long arm of chromosome 7. Based on the various breakpoints in prior studies, a number of phenotypic variations have been identified that are unique to each of the reports. However, there are also a number of similarities among these cases as well. We hope to provide a concise review of the literature and genes involved within our deletion sequence in the hope that it will contribute to creating a phenotypic profile for this patient population.

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

    Science.gov (United States)

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

    2017-05-01

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

  9. Smoking is associated with severity of liver fibrosis but not with histological severity in nonalcoholic fatty liver disease. Results from a cross-sectional study.

    Science.gov (United States)

    Munsterman, Isabelle D; Smits, Mark M; Andriessen, Rene; van Nieuwkerk, Carin M J; Bloemena, Elisabeth; Mulder, Chris J J; Tjwa, Eric T T L; van Geenen, Erwin J M

    2017-08-01

    To assess the influence of smoking on histological disease severity and fibrosis in real-world NAFLD patients. Consecutive NAFLD patients were identified with liver biopsies performed between 2008 and 2015. Characteristics such as smoking status and total number of pack years were collected. Biopsies were revised and BRUNT fibrosis and NAFLD activity score (NAS) determined. Patients with a high NAS (≥5) were compared to patients with a low NAS (smoking (current or past smoker) were defined ever smokers. Fifty-six patients were included (mean age 49 ± 14.3, 68.9% males and 39.3% history of smoking). Ever smokers had a higher fibrosis score than never smokers; two (IQR 0-3) versus one (IQR 1-1.5) (p = .040). Patients with advanced fibrosis smoked significantly more pack years than patients with no-early fibrosis; 10.6 (IQR 0-25.8) versus 0 (IQR 0-7) (p = .011). There is a weak to moderate correlation between fibrosis stage and number of pack years (Spearman's Rho = 0.341, p = .012). There was no difference in NAS between never and ever smokers; 2.8 ± 1.5 versus 3.3 ± 1.4 (p = .205). Patients with NAS Smoking is associated with severity of NAFLD-related liver fibrosis but not with histological disease severity. This supports the recommendation to cease smoking for NAFLD patients.

  10. Desquamative interstitial pneumonia: A case report

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    Lovrenski Aleksandra

    2014-01-01

    Full Text Available Introduction. Desquamative interstitial pneumonia is one of the rarest idiopathic interstitial pneumonias and the rarest form of smoking-related interstitial lung diseases. It was first described by Liebow in 1965. Histologically, it is characterized by the presence of eosinophilic macrophages uniformly filling airspaces which often contain a finely granular light-brown pigment that does not stain for hemosiderin. The alveolar walls are usually mildly thickened by fibrous tissue and infiltrated by a moderate number of lymphocytes. Case Outline. Our patient was a 56-year-old male, heavy smoker, with bilateral lung infiltrations of unknown etiology and several months of discomfort in the form of dry cough and shortness of breath. Lung function tests showed a moderate restrictive ventilation disorder and a severe reduction of diffusing capacity. Since bronchoscopic specimens did not reveal lung lesion etiology, an open lung biopsy of the lower left pulmonary lobe was performed, and based on the obtained surgical material the pathohistologically diagnosis of desquamative interstitial pneumonia was established. The patient was started on corticosteroid and immunosuppressive therapy, and he ceased smoking. At the last control examination, two years after the onset of symptoms, the patient was feeling well, and high-resolution computed tomography (HRCT scan of the thorax showed regression of pathological changes. Conclusion. Although, as in our case, the majority of DIP patients improve on treatment, some patients still develop progressive irreversible fibrosis despite therapy.

  11. CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity

    Science.gov (United States)

    Blaisdell, Carol J; Howard, Timothy D; Stern, Augustus; Bamford, Penelope; Bleecker, Eugene R; Stine, O Colin

    2004-01-01

    Background Cystic fibrosis (CF) lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs) in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. Methods The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1) > 70% and < 40%). Results PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. Conclusions CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity. PMID:15507145

  12. CLC-2 single nucleotide polymorphisms (SNPs as potential modifiers of cystic fibrosis disease severity

    Directory of Open Access Journals (Sweden)

    Bleecker Eugene R

    2004-10-01

    Full Text Available Abstract Background Cystic fibrosis (CF lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. Methods The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1 > 70% and Results PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. Conclusions CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity.

  13. Differentiation of several interstitial lung disease patterns in HRCT images using support vector machine: role of databases on performance

    Science.gov (United States)

    Kale, Mandar; Mukhopadhyay, Sudipta; Dash, Jatindra K.; Garg, Mandeep; Khandelwal, Niranjan

    2016-03-01

    Interstitial lung disease (ILD) is complicated group of pulmonary disorders. High Resolution Computed Tomography (HRCT) considered to be best imaging technique for analysis of different pulmonary disorders. HRCT findings can be categorised in several patterns viz. Consolidation, Emphysema, Ground Glass Opacity, Nodular, Normal etc. based on their texture like appearance. Clinician often find it difficult to diagnosis these pattern because of their complex nature. In such scenario computer-aided diagnosis system could help clinician to identify patterns. Several approaches had been proposed for classification of ILD patterns. This includes computation of textural feature and training /testing of classifier such as artificial neural network (ANN), support vector machine (SVM) etc. In this paper, wavelet features are calculated from two different ILD database, publically available MedGIFT ILD database and private ILD database, followed by performance evaluation of ANN and SVM classifiers in terms of average accuracy. It is found that average classification accuracy by SVM is greater than ANN where trained and tested on same database. Investigation continued further to test variation in accuracy of classifier when training and testing is performed with alternate database and training and testing of classifier with database formed by merging samples from same class from two individual databases. The average classification accuracy drops when two independent databases used for training and testing respectively. There is significant improvement in average accuracy when classifiers are trained and tested with merged database. It infers dependency of classification accuracy on training data. It is observed that SVM outperforms ANN when same database is used for training and testing.

  14. Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Bartis, Domokos; Crowley, Louise E; D'Souza, Vijay K; Borthwick, Lee; Fisher, Andrew J; Croft, Adam P; Pongrácz, Judit E; Thompson, Richard; Langman, Gerald; Buckley, Christopher D; Thickett, David R

    2016-04-14

    CD248 or Endosialin is a transmembrane molecule expressed in stromal cells binding to extracellular matrix (ECM) components. It has been previously implicated in kidney fibrosis, rheumatoid arthritis as well as in tumour-stromal interactions. This study investigates the role of CD248 in the pathogenesis of fibrotic diseases in Idiopathic Pulmonary Fibrosis (IPF). CD248 quantitative immunohistochemistry (IHC) was performed on lung samples from 22 IPF patients and its expression was assayed in cultured pulmonary fibroblasts and epithelial cells. Effects of CD248 silencing was evaluated on fibroblast proliferation and myofibroblast differentiation. IHC revealed strong CD248 expression in mesenchymal cells of normal lung structures such as pleura and adventitia but not in epithelium. Fibrotic areas showed markedly stronger staining than unaffected lung tissue. The extent of CD248 staining showed a significant negative correlation to lung function parameters FEV1, FVC, TLC, and TLCO (r2 > 0 · 35, p < 0 · 01). CD248 protein levels were significantly greater in IPF-derived lung fibroblasts vs normal lung fibroblasts (p < 0 · 01) and CD248 silencing significantly reduced the proliferation of lung fibroblasts, but did not affected myofibroblast differentiation. We conclude that CD248 overexpression is possibly involved in the pathogenesis of IPF and it has potential as a disease severity marker. Given that CD248 ligands are collagen type I, IV and fibronectin, we hypothesise that CD248 signalling represents a novel matrix-fibroblast interaction that may be a potential therapeutic target in IPF.

  15. The ACE gene D/I polymorphism as a modulator of severity of cystic fibrosis

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    Marson Fernando A L

    2012-08-01

    Full Text Available Abstract Background Cystic Fibrosis (CF is a monogenic disease with complex expression because of the action of genetic and environmental factors. We investigated whether the ACE gene D/I polymorphism is associated with severity of CF. Methods A cross-sectional study was performed, from 2009 to 2011, at University of Campinas – UNICAMP. We analyzed 180 patients for the most frequent mutations in the CFTR gene, presence of the ACE gene D/I polymorphism and clinical characteristics of CF. Results There was an association of the D/D genotype with early initiation of clinical manifestations (OR: 1.519, CI: 1.074 to 2.146, bacterium Burkholderia cepacia colonization (OR: 3.309, CI: 1.476 to 6.256 and Bhalla score (BS (p = 0.015. The association was observed in subgroups of patients which were defined by their CFTR mutation genotype (all patients; subgroup I: no mutation detected; subgroup II: one CFTR allele identified to mutation class I, II or III; subgroup III: both CFTR alleles identified to mutation class I, II and/or III. Conclusion An association between the D allele in the ACE gene and the severity of CF was found in our study.

  16. Smoking-related interstitial lung diseases

    International Nuclear Information System (INIS)

    Marten, K.

    2007-01-01

    The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis

  17. An approach to interstitial lung disease in India

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    J N Pande

    2014-07-01

    Full Text Available Interstitial lung diseases are common and have varied etiology, clinical presentation, clinical course and outcome. They pose a diagnostic challenge to physicians and pulmonologists. Patients present with dry cough, exertional dyspnoea, interstitial lesions on X-ray of the chest and restrictive ventilatory defect on spirometry. A sharp decline in oxygen saturation with exercise is characteristic. Careful evaluation of the history of the patient and physical examination help in narrowing down diagnostic probabilities. HRCT of the chest has emerged as an important tool in the evaluation of these disorders. Idiopathic Interstitial Pneumonias (IIP are a group of conditions which are classified into several types based on pathological features. Bronchoscopic procedures are helpful in diagnosis of certain disorders but are of limited value in classification of IIP which requires surgical biopsy. Usual Interstitial Pneumonia (UIP, also referred to as Idiopathic Pulmonary Fibrosis, has a progressive course and an unfavourable outcome. Certain new drugs have recently become available for treatment of UIP. Our approach towards diagnosis and management of interstitial lung diseases based on personal experience over the past three decades is reported here. Key words: Usual interstitial pneumonia – sarcoidosis – pneumoconiosis – bronchoscopy – lung biopsy 

  18. Interstitial nephritis.

    Science.gov (United States)

    Papper, S

    1980-01-01

    There are many causes of interstitial nephritis other than pyelonephritis. The term interstitial nephritis does not connote a single etiologic or pathogenetic mechanism; it rather arbitrarily places together a wider variety of renal diseases that have a predilection for early and major involvement of the renal interstitium. The prototype of acute interstitial nephritis is acute pyelonephritis. In addition, there is a drug-related acute interstitial disease that is probably of immunological nature and usually reverses with discontinuance of the offending drug. Chronic interstitial nephritis includes many diverse illnesses. Nonobstructive pyelonephritis occurs but its prevalence is debated. Analgesic abuse nephropathy is not rare and is potentially reversible. Papillary necrosis has many causes and a wide spectrum of clinical presentations. Heavy metals, such as lead, cause interstitial nephritis. Balkan nephropathy occurs in an endemic area and although not bacterial in origin is of unknown cause.

  19. The use of trypsin-like blood activity as a marker of pulmonary fibrosis severity.

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    V. V. Rodionova

    2018-05-01

    Full Text Available Purpose – to determine changes in the trypsin-like blood activity and its relationship with acute phase indices of inflammation in patients with pulmonary fibrosis (PF as a marker of course severity and prognosis of the disease. Materials and Methods: The study included 18 patients: 15 (83% women and 3 (17% men, mean age 53±2.5 years. The control group included 15 practically healthy persons. All the examined patients (n=18 were divided into two groups: with mild or moderately severe PF – 8 (44.4% patients (group I, severe PF – 10 (55.6% of patients (group II. Duration of the disease - from 1 month. up to 4 years. Patients underwent clinic-laboratory and anthropometric studies, a mMRC questionnaire was used, blood saturation was measured, lung radiography in 2 projections, echocardiography, and if necessary a high-resolution computer tomography etc were performed. Results and discussion: More than half of the patients were overweight (44,4% or had obesity of І-ІІІ st. (27.8%. The severity of dyspnea according to mMRC scale was 3.0 (3.0-4.0 points in patients of group II and 2.5 (2.0-3.0 points in patients of group I. There was a decrease in C-reactive protein (CRP in group I and a tendency to increase in patients of group II. When analyzing the indicator of trypsin-like blood activity (TLA, it was found that the median TLA at the beginning of the observation was twice as high as in healthy individuals, direct correlation was established between the level of TLA and the severity of the disease course. After treatment the level of TLA decreased in group I patients. In the severe course of PF, the average TLA level remained high. The progredient course of LF is characterized by severe clinical symptoms, a significant increase in TLA, CRP, reduced O2 saturation, a lack of response to treatment and an unfavorable prognosis. The TLA index can be used as a biochemical marker of the severity of PF along with the CRPindex, O2 saturation and

  20. Normal Lung Quantification in Usual Interstitial Pneumonia Pattern: The Impact of Threshold-based Volumetric CT Analysis for the Staging of Idiopathic Pulmonary Fibrosis.

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    Hirotsugu Ohkubo

    Full Text Available Although several computer-aided computed tomography (CT analysis methods have been reported to objectively assess the disease severity and progression of idiopathic pulmonary fibrosis (IPF, it is unclear which method is most practical. A universal severity classification system has not yet been adopted for IPF.The purpose of this study was to test the correlation between quantitative-CT indices and lung physiology variables and to determine the ability of such indices to predict disease severity in IPF.A total of 27 IPF patients showing radiological UIP pattern on high-resolution (HR CT were retrospectively enrolled. Staging of IPF was performed according to two classification systems: the Japanese and GAP (gender, age, and physiology staging systems. CT images were assessed using a commercially available CT imaging analysis workstation, and the whole-lung mean CT value (MCT, the normally attenuated lung volume as defined from -950 HU to -701 Hounsfield unit (NL, the volume of the whole lung (WL, and the percentage of NL to WL (NL%, were calculated.CT indices (MCT, WL, and NL closely correlated with lung physiology variables. Among them, NL strongly correlated with forced vital capacity (FVC (r = 0.92, P <0.0001. NL% showed a large area under the receiver operating characteristic curve for detecting patients in the moderate or advanced stages of IPF. Multivariable logistic regression analyses showed that NL% is significantly more useful than the percentages of predicted FVC and predicted diffusing capacity of the lungs for carbon monoxide (Japanese stage II/III/IV [odds ratio, 0.73; 95% confidence intervals (CI, 0.48 to 0.92; P < 0.01]; III/IV [odds ratio. 0.80; 95% CI 0.59 to 0.96; P < 0.01]; GAP stage II/III [odds ratio, 0.79; 95% CI, 0.56 to 0.97; P < 0.05].The measurement of NL% by threshold-based volumetric CT analysis may help improve IPF staging.

  1. Normal Lung Quantification in Usual Interstitial Pneumonia Pattern: The Impact of Threshold-based Volumetric CT Analysis for the Staging of Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Ohkubo, Hirotsugu; Kanemitsu, Yoshihiro; Uemura, Takehiro; Takakuwa, Osamu; Takemura, Masaya; Maeno, Ken; Ito, Yutaka; Oguri, Tetsuya; Kazawa, Nobutaka; Mikami, Ryuji; Niimi, Akio

    2016-01-01

    Although several computer-aided computed tomography (CT) analysis methods have been reported to objectively assess the disease severity and progression of idiopathic pulmonary fibrosis (IPF), it is unclear which method is most practical. A universal severity classification system has not yet been adopted for IPF. The purpose of this study was to test the correlation between quantitative-CT indices and lung physiology variables and to determine the ability of such indices to predict disease severity in IPF. A total of 27 IPF patients showing radiological UIP pattern on high-resolution (HR) CT were retrospectively enrolled. Staging of IPF was performed according to two classification systems: the Japanese and GAP (gender, age, and physiology) staging systems. CT images were assessed using a commercially available CT imaging analysis workstation, and the whole-lung mean CT value (MCT), the normally attenuated lung volume as defined from -950 HU to -701 Hounsfield unit (NL), the volume of the whole lung (WL), and the percentage of NL to WL (NL%), were calculated. CT indices (MCT, WL, and NL) closely correlated with lung physiology variables. Among them, NL strongly correlated with forced vital capacity (FVC) (r = 0.92, P <0.0001). NL% showed a large area under the receiver operating characteristic curve for detecting patients in the moderate or advanced stages of IPF. Multivariable logistic regression analyses showed that NL% is significantly more useful than the percentages of predicted FVC and predicted diffusing capacity of the lungs for carbon monoxide (Japanese stage II/III/IV [odds ratio, 0.73; 95% confidence intervals (CI), 0.48 to 0.92; P < 0.01]; III/IV [odds ratio. 0.80; 95% CI 0.59 to 0.96; P < 0.01]; GAP stage II/III [odds ratio, 0.79; 95% CI, 0.56 to 0.97; P < 0.05]). The measurement of NL% by threshold-based volumetric CT analysis may help improve IPF staging.

  2. Smoking-related interstitial lung diseases: histopathological and imaging perspectives

    International Nuclear Information System (INIS)

    Desai, S.R.; Ryan, S.M.; Colby, T.V.

    2003-01-01

    The present review focuses on the interstitial lung diseases related to smoking. Thus, the pathology and radiology of Langerhans cell histiocytosis, desquamative interstitial pneumonia, respiratory bronchiolitis and respiratory bronchiolitis-associated-interstitial lung disease are considered. The more tenuous association between pulmonary fibrosis and smoking is also discussed

  3. Smoking-related interstitial lung diseases: histopathological and imaging perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Desai, S.R.; Ryan, S.M.; Colby, T.V

    2003-04-01

    The present review focuses on the interstitial lung diseases related to smoking. Thus, the pathology and radiology of Langerhans cell histiocytosis, desquamative interstitial pneumonia, respiratory bronchiolitis and respiratory bronchiolitis-associated-interstitial lung disease are considered. The more tenuous association between pulmonary fibrosis and smoking is also discussed.

  4. Is sweat chloride predictive of severity of cystic fibrosis lung disease assessed by chest computed tomography?

    Science.gov (United States)

    Caudri, Daan; Zitter, David; Bronsveld, Inez; Tiddens, Harm

    2017-09-01

    Cystic Fibrosis (CF) lung disease is characterized by a marked heterogeneity. Sweat chloride-level is a functional marker of the CF Transmembrane Regulator (CFTR) protein and could be an important predictor of later disease severity. In this retrospective analysis children from the Rotterdam CF clinic with available sweat chloride level at diagnosis and at least one routine spirometry-controlled volumetric chest CT scan in follow-up were included. CT scans were scored using the CF-CT scoring system (% of maximum). Associations between sweat chloride-levels and CF-CT scores were calculated using linear regression models, adjusting for age at sweat test and age at follow-up. Because structural lung damage develops over the course of many years, effect modification by the age at follow-up CT-scan was tested for by age-stratification. In 59 children (30 male) sweat chloride was measured at diagnosis (median age 0.5 years, range 0-13) and later chest CT performed (median age 14 years, range 6-18). Sweat chloride was associated with significantly higher CT-CT total score, bronchiectasis score, and mucus plugging score. Stratification for age at follow-up in tertiles showed this association remained only in the oldest age group (range 15-18 years). In that subgroup associations were found with all but one of the CF-CT subscores, as well as with all tested lung functions parameters. Sweat chloride-level is a significant predictor of CF lung disease severity as determined by chest CT and lung function. This association could only be demonstrated in children with follow-up to age 15 years and above. © 2017 Wiley Periodicals, Inc.

  5. Tracheomalacia in adults with cystic fibrosis: determination of prevalence and severity with dynamic cine CT.

    LENUS (Irish Health Repository)

    McDermott, Shaunagh

    2012-02-01

    PURPOSE: To determine the prevalence and severity of tracheomalacia in adults with cystic fibrosis (CF) by using dynamic cine multidetector computed tomography (CT) and to correlate these findings with pulmonary function test (PFT) results and the severity of parenchymal lung disease. MATERIALS AND METHODS: In this institutional review board-approved HIPAA-compliant study, 40 patients with CF (22 men, 18 women; mean age, 28 years +\\/- 8 [standard deviation]; age range, 18-54 years) prospectively underwent PFTs, standard thin-section CT, and two dynamic cine multidetector CT acquisitions. Ten control subjects underwent dynamic cine multidetector CT. After standard thin-section CT was completed, dynamic cine multidetector CT was performed during a forced expiratory maneuver and during coughing. Dynamic cine multidetector CT images in nine patients were excluded. Maximal inspiratory, dynamic expiratory, and end-expiratory tracheal luminal areas were compared (Student t test) and correlated (Spearman rank) with PFT results and severity of parenchymal lung disease. RESULTS: Mean predicted forced expiratory volume in 1 second (FEV(1)) was 70.6% +\\/- 20.7, and mean Bhalla CT score was 41.8% +\\/- 13.6. In patients with CF, dynamic cine mean tracheal cross-sectional area reduction was 51.7% +\\/- 18.4 (range, 9%-89%) for forced expiratory maneuvers and 68.8% +\\/- 11.7 (range, 18%-88%) for coughing (P = .001). Tracheomalacia was demonstrated in 24 (69%) patients and no control subjects during forced expiratory maneuvers (P = .001) and in 10 (29%) patients and one (10%) control subject during coughing. For end-expiration images, mean tracheal luminal reduction was 16.1% +\\/- 14.0% (range, 0.0%-53.0%), with one patient demonstrating tracheal luminal reduction of more than 50%. There was no correlation between tracheal cross-sectional luminal reduction and either predicted FEV(1) or CT Bhalla score. CONCLUSION: Tracheomalacia depicted at dynamic cine multidetector CT is a

  6. The diffuse interstitial lung disease - with emphasis in the idiopathic interstitial pneumonias

    International Nuclear Information System (INIS)

    Bustillo P, Jose G; Pacheco, Pedro M; Matiz, Carlos; Ojeda, Paulina; Carrillo B, Jorge A.

    2003-01-01

    The term diffuse interstitial lung disease, it refers to those diseases that commit the interstice basically, the space between the membrane basal epithelial and endothelial, although the damage can also commit the outlying air spaces and the vessels; the supplement is centered in the diffuse interstitial lung illness of unknown cause; well-known as idiopathic interstitial pneumonias, making emphasis in the more frequents, the pulmonary fibrosis idiopathic or cryptogenic fibrosant alveolitis

  7. Pathogenesis of Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

  8. Breath Alkane as an index of severity for oral submucous fibrosis: A new perspective?

    NARCIS (Netherlands)

    Arakeri, G.; Boraks, G.; Aljabab, A.S.; Patil, S.G.; Merkx, M.A.W.; Brennan, P.A.

    2017-01-01

    Oral submucous fibrosis (OSMF) is a devastating disease commonly seen in the Asian subcontinent that results in significant functional morbidity for patients and has a high potential for malignant transformation. Over the last three decades, different diagnostic methods have been described to

  9. Interstitial cystitis

    Science.gov (United States)

    ... symptoms get better. Reduce or stop consuming caffeine, chocolate, carbonated beverages, citrus drinks, and foods with a ... rarely done anymore Support Groups Some people may benefit from taking part in interstitial cystitis support groups . ...

  10. Interstitial Cystitis

    Science.gov (United States)

    ... relieve symptoms. Diet. Alcohol, tomatoes, spices, carbonated drinks, chocolate, caffeine, citrus fruits and drinks, pickled foods, artificial ... at scheduled times and using relaxation techniques. Physical therapy. People who have interstitial cystitis may have painful ...

  11. 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.

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

    International Nuclear Information System (INIS)

    Qi, Q.; Li, T.; Li, J.C.; Li, Y.

    2015-01-01

    The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m 2 ), normal weight (18.5≤BMI<25.0 kg/m 2 ), overweight (25.0≤BMI<30.0 kg/m 2 ), and obese (BMI≥30.0 kg/m 2 ). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m 2 . The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ 2 =35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis

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

    Directory of Open Access Journals (Sweden)

    Q. Qi

    2015-08-01

    Full Text Available The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m2, normal weight (18.5≤BMI<25.0 kg/m2, overweight (25.0≤BMI<30.0 kg/m2, and obese (BMI≥30.0 kg/m2. Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m2. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ2=35.16, P<0.001. The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis.

  14. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Kowdley, Kris V; Belt, Patricia; Wilson, Laura A; Yeh, Matthew M; Neuschwander-Tetri, Brent A; Chalasani, Naga; Sanyal, Arun J; Nelson, James E

    2012-01-01

    Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P 1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P 1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis. Copyright © 2011 American Association for the Study of Liver Diseases.

  15. Interstitial Features at Chest CT Enhance the Deleterious Effects of Emphysema in the COPDGene Cohort.

    Science.gov (United States)

    Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Rahaghi, Farbod N; Sanchez-Ferrero, Gonzalo Vegas; Putman, Rachel K; Hunninghake, Gary M; Onieva, Jorge Onieva; Martinez, Fernando J; Choi, Augustine M; Bowler, Russell P; Lynch, David A; Hatabu, Hiroto; Bhatt, Surya P; Dransfield, Mark T; Wells, J Michael; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R

    2018-06-05

    Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features

  16. Ketamine induced renal fibrosis in a ketamine addition rat model

    Directory of Open Access Journals (Sweden)

    Mei-Yu Jang

    2017-09-01

    Conclusion: Ketamine treatment not only induced cystitis-like syndrome, but also renal fibrosis. These renal interstitial fibrosis changes may be induced by the TGF-β pathway. These preliminary results can provide valuable information from a clinical perspective.

  17. Interstitial lung disease: Diagnostic approach

    OpenAIRE

    Kaushik Saha

    2014-01-01

    Interstitial lung disease (ILD) is a final common pathway of a broad heterogeneous group of parenchymal lung disorders. It is characterized by progressive fibrosis of the lung leading to restriction and diminished oxygen transfer. Clinically, the presenting symptoms of ILD are non-specific (cough and progressive dyspnea on exertion) and are often attributed to other diseases, thus delaying diagnosis and timely therapy. Clues from the medical history along with the clinical context and radiolo...

  18. Avaliação de parâmetros histológicos na pneumonia intersticial usual (fibrose pulmonar idiopática Evaluation of the histological parameters in usual interstitial pneumonia (idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    RIMARCS GOMES FERREIRA

    2000-12-01

    Full Text Available A fibrose pulmonar idiopática (alveolite fibrosante criptogênica é uma doença pulmonar intersticial progressiva de etiologia desconhecida, morfologicamente reconhecida como pneumonia intersticial usual. Desde a publicação de Hamman e Rich (1944 até os dias atuais, uma das grandes preocupações foi a tentativa de encontrar um marcador histológico para correlacionar com prognóstico e resposta terapêutica. A busca desta situação não tem sido muito alentadora, pois existem vários pontos duvidosos na patogênese desta doença. Admite-se que a resposta terapêutica desta entidade se relaciona com a celularidade e fibrose presentes no tecido. A proposta deste estudo é descrever os resultados de método semiquantitativo segundo a avaliação independente de dois patologistas, das alterações exsudativo-inflamatórias, reparativo-fibróticas e de vias aéreas, em 24 pacientes com diagnóstico de fibrose pulmonar idiopática, submetidos à biópsia a céu aberto. Foram analisados 14 parâmetros histológicos segundo escala de 0 a 5 para as alterações intersticiais e de 0 a 2 para o comprometimento de vias aéreas e de espaços aéreos. Da análise independente realizada pelos dois observadores constatou-se concordância significante em todas as variáveis histológicas com Kw (teste de Kappa indo de 0,47 a 0,92. Apenas na análise da intensidade da inflamação septal as discordâncias também foram significantes, sugerindo que para este parâmetro a percentagem de comprometimento tecidual deve ser previamente discutida entre os observadores. O método utilizado demonstrou ser rápido e eficiente.Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis is a progressive interstitial pulmonary disease of unknown etiology. Since Hamman's and Rich's (1944 reports, many studies have tried to find a histological marker for the correlation between prognosis and response to therapy. However, there are many doubts regarding pathogenesis

  19. Serial changes and prognostic implications of CT findings in combined pulmonary fibrosis and emphysema: comparison with fibrotic idiopathic interstitial pneumonias alone.

    Science.gov (United States)

    Lee, Geewon; Kim, Ki Uk; Lee, Ji Won; Suh, Young Ju; Jeong, Yeon Joo

    2017-05-01

    Background Although fibrotic idiopathic interstitial pneumonias (IIPs) alone and those combined with pulmonary emphysema are naturally progressive diseases, the process of deterioration and outcomes are variable. Purpose To evaluate and compare serial changes of computed tomography (CT) abnormalities and prognostic predictive factors in fibrotic IIPs alone and those combined with pulmonary emphysema. Material and Methods A total of 148 patients with fibrotic IIPs alone (82 patients) and those combined with pulmonary emphysema (66 patients) were enrolled. Semi-quantitative CT analysis was used to assess the extents of CT characteristics which were evaluated on initial and follow-up CT images. Univariate and multivariate analyses were performed to assess the effects of clinical and CT variables on survival. Results Significant differences were noted between fibrotic scores, as determined using initial CT scans, in the fibrotic IIPs alone (21.22 ± 9.83) and those combined with pulmonary emphysema groups (14.70 ± 7.28) ( P pulmonary emphysema group. Multivariate Cox proportional hazards analysis showed changes in the extent of GGO (hazard ratio, 1.056) and the presence of lung cancer (hazard ratio, 4.631) were predictive factors of poor survivals. Conclusion Although patients with fibrotic IIPs alone and those combined with pulmonary emphysema have similar mortalities, lung cancer was more prevalent in patients with fibrotic IIPs combined with pulmonary emphysema. Furthermore, changes in the extent of GGO and the presence of lung cancer were independent prognostic factors of poor survivals.

  20. Severe bone demineralisation is associated with higher mortality in children with cystic fibrosis.

    LENUS (Irish Health Repository)

    O'Reilly, R

    2009-02-01

    Decreased bone mineral density (BMD) is an emerging problem for clinicians who care for children with Cystic fibrosis (CF). The aim of this study was to determine prevalence and assess risk factors for reduced BMD in our adolescent population with CF. All bone densitometry scans (n=99) performed on children (n=79) with a mean age 13.6 (10-19.2) years over a 7 year period (2000-2007) were reviewed. Patient records were reviewed for correlating clinical data. Low BMD is frequently present in adults and children with variable reports (36-66%). In our study, BMD expressed as z score of L2-L4 spine was reduced in a total of 50% children with a preponderance of males. Bone demineralization was strongly associated with increasing age (p=0.03), diminished lung function (p=0.027), reduced body mass index (p=0.001) and treatment with oral corticosteroids (p=0.02).

  1. Calcium Channel Blockers and Esophageal Sclerosis: Should We Expect Exacerbation of Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Charalampos Seretis

    2012-01-01

    Full Text Available Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome.

  2. Thin-section computed tomography–histopathologic comparisons of pulmonary focal interstitial fibrosis, atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma with pure ground-glass opacity

    Energy Technology Data Exchange (ETDEWEB)

    Si, Ming-Jue, E-mail: smjsh@hotmail.com [Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 280, Mohe Road, Shanghai 201999 (China); Tao, Xiao-Feng, E-mail: taoxiaofeng1963@hotmail.com [Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 280, Mohe Road, Shanghai 201999 (China); Du, Guang-Ye, E-mail: 715376158@qq.com [Department of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 280, Mohe Road, Shanghai 201999 (China); Cai, Ling-Ling, E-mail: caill_00@163.com [Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 280, Mohe Road, Shanghai 201999 (China); Han, Hong-Xiu, E-mail: hanhongxiu@hotmail.com [Department of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 280, Mohe Road, Shanghai 201999 (China); Liang, Xi-Zi, E-mail: liangxizish@hotmail.com [Department of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 280, Mohe Road, Shanghai 201999 (China); Zhao, Jiang-Min, E-mail: zhaojiangmin1962@hotmail.com [Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No. 280, Mohe Road, Shanghai 201999 (China)

    2016-10-15

    Objective: To retrospectively compare focal interstitial fibrosis (FIF), atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA) with pure ground-glass opacity (GGO) using thin-section computed tomography (CT). Materials and methods: Sixty pathologically confirmed cases were reviewed including 7 cases of FIF, 17 of AAH, 23of AIS, and 13 of MIA. All nodules kept pure ground glass appearances before surgical resection and their last time of thin-section CT imaging data before operation were collected. Differences of patient demographics and CT features were compared among these four types of lesions. Results: FIF occurred more frequently in males and smokers while the others occurred more frequently in female nonsmokers. Nodule size was significant larger in MIA (P < 0.001, cut-off value = 7.5 mm). Nodule shape (P = 0.045), margin characteristics (P < 0.001), the presence of pleural indentation (P = 0.032), and vascular ingress (P < 0.001) were significant factors that differentiated the 4 groups. A concave margin was only demonstrated in a high proportion of FIF at 85.7% (P = 0.002). There were no significant differences (all P > 0.05) in age, malignant history, attenuation value, location, and presence of bubble-like lucency. Conclusion: A nodule size >7.5 mm increases the possibility of MIA. A concave margin could be useful for differentiation of FIF from the other malignant or pre-malignant GGO nodules. The presence of spiculation or pleural indentation may preclude the diagnosis of AAH.

  3. Smoking-related interstitial lung diseases; Interstitielle Lungenerkrankungen bei Rauchern

    Energy Technology Data Exchange (ETDEWEB)

    Marten, K. [Technische Univ. Muenchen (Germany). Klinikum rechts der Isar, Inst. fuer Roentgendiagnostik

    2007-03-15

    The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis.

  4. Nephrogenic Systemic Fibrosis Risk After Liver Magnetic Resonance Imaging With Gadoxetate Disodium in Patients With Moderate to Severe Renal Impairment

    Science.gov (United States)

    Lauenstein, Thomas; Ramirez-Garrido, Francisco; Kim, Young Hoon; Rha, Sung Eun; Ricke, Jens; Phongkitkarun, Sith; Boettcher, Joachim; Gupta, Rajan T.; Korpraphong, Pornpim; Tanomkiat, Wiwatana; Furtner, Julia; Liu, Peter S.; Henry, Maren; Endrikat, Jan

    2015-01-01

    Objective The objective of this study was to assess the risk of gadoxetate disodium in liver imaging for the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal impairment. Materials and Methods We performed a prospective, multicenter, nonrandomized, open-label phase 4 study in 35 centers from May 2009 to July 2013. The study population consisted of patients with moderate to severe renal impairment scheduled for liver imaging with gadoxetate disodium. All patients received a single intravenous bolus injection of 0.025-mmol/kg body weight of liver-specific gadoxetate disodium. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. Results A total of 357 patients were included, with 85 patients with severe and 193 patients with moderate renal impairment, which were the clinically most relevant groups. The mean time period from diagnosis of renal disease to liver magnetic resonance imaging (MRI) was 1.53 and 5.46 years in the moderate and severe renal impairment cohort, respectively. Overall, 101 patients (28%) underwent additional contrast-enhanced MRI with other gadolinium-based MRI contrast agents within 12 months before the start of the study or in the follow-up. No patient developed symptoms conclusive of NSF within the 2-year follow-up. Conclusions Gadoxetate disodium in patients with moderate to severe renal impairment did not raise any clinically significant safety concern. No NSF cases were observed. PMID:25756684

  5. Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression

    Directory of Open Access Journals (Sweden)

    Hirani Nikhil

    2010-10-01

    Full Text Available Abstract Background A significant genetic component has been described for idiopathic pulmonary fibrosis (IPF. The R131H (rs1801274 polymorphism of the IgG receptor FcγRIIa determines receptor affinity for IgG subclasses and is associated with several chronic inflammatory diseases. We investigated whether this polymorphism is associated with IPF susceptibility or progression. Methods In a case-control study, we compared the distribution of FcγRIIa R131H genotypes in 142 patients with IPF and in 218 controls using allele-specific PCR amplification. Results No differences in the frequency of FcγRIIa genotypes were evident between IPF patients and control subjects. However, significantly impaired pulmonary function at diagnosis was observed in HH compared to RR homozygotes, with evidence of more severe restriction (reduced forced vital capacity (FVC and lower diffusing capacity for carbon monoxide (DLCO. Similarly, increased frequency of the H131 allele was observed in patients with severe disease (DLCO 10% drop in FVC and/or > 15% fall in DLCO at 12 months after baseline (0.48 vs. 0.33; p = 0.023. Conclusions These findings support an association between the FcγRIIa R131H polymorphism and IPF severity and progression, supporting the involvement of immunological mechanisms in IPF pathogenesis.

  6. A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay.

    Science.gov (United States)

    Liang, Liyang; Xie, Yingjun; Shen, Yiping; Yin, Qibin; Yuan, Haiming

    2016-01-01

    Proximal 4p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafe-au-lait spots, developmental delay, tall and thin habitus, and intellectual disability. At present, over 20 cases of this syndrome have been published. However, duplication of the same region in proximal 4p has never been reported. Here, we describe a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre- and postnatal developmental delay, and mild cognitive impairments. A de novo 4.5-Mb interstitial duplication at 4p15.2p15.1 was detected by chromosomal microarray analysis. Next-generation sequencing was employed and confirmed the duplication, but revealed no additional pathogenic variants. Several candidate genes in this interval responsible for the complex clinical phenotype were identified, such as RBPJ, STIM2, CCKAR, and LGI2. The results suggest a novel contiguous gene duplication syndrome. © 2016 S. Karger AG, Basel.

  7. Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection

    Directory of Open Access Journals (Sweden)

    Sophie Seang

    2017-06-01

    Conclusions: Circulating LOXL2 levels may be a noninvasive measure of intestinal fibrosis and GALT CD4+T lymphocyte depletion in treated HIV infection. LOXL2 crosslinks elastin and collagen, and elevated LOXL2 levels occur in pathologic states, making LOXL2 inhibition a potential interventional target for intestinal fibrosis and its sequelae.

  8. Procollagen Type I and III Aminoterminal Propeptide Levels and Severity of Interstitial Lung Disease in Mexican Women With Progressive Systemic Sclerosis.

    Science.gov (United States)

    Gonzalez-Lopez, Laura; Rocha-Muñoz, Alberto D; Olivas-Flores, Eva M; Garcia-Gonzalez, Araceli; Peguero-Gómez, Ana R; Flores-Navarro, Juan; Villa-Manzano, Alberto I; Zavaleta-Muñiz, Soraya A; Salazar-Paramo, Mario; Mejía, Mayra; Juárez-Contreras, Pablo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, Ernesto G; Trujillo-Hernández, Benjamin; Nava-Zavala, Arnulfo H; Gamez-Nava, Jorge I

    2015-09-01

    Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases. To evaluate whether serum levels of procollagen typei and iii aminoterminal propeptide (PINP and PIIINP) correlate with severity and patterns of ILD in Mexican women with SSc. Thirty three SSc patients were assessed for disease characteristics and anti-topoisomerase antibodies (topoi), and also underwent pulmonary function tests and high-resolution computed tomography (HRCT). Nineteen patients had ILD+SSc, and 14 had no lung involvement (no ILD-SSc); data were compared with those from 45 healthy controls. PINP and PIIINP were assessed in all 3 groups. Patients with SSc had higher PINP and PIIINP vs controls (P=.001, P<.001, respectively). Compared to no ILD-SSc patients, those with ILD+SSc had longer disease duration in years (P=.005), higher modified Rodnan skin score (P<.001), higher Health Assessment Questionnaire-Disability-Index scores (P<.001), higher topoi U/mL (P<.001), PINP (49.28±28.63 vs. 32.12±18.58μg/L, P=.05), and PIIINP (4.33±1.03 vs. 2.67±1.26μg/L, P<.001) levels. ILD severity based on total HRCT correlated with PINP (r=.388, P=.03) and PIIINP (P=.594, P<.001). On adjusted analysis, ILD severity was associated with disease duration (P=.037), PIIINP (P=.038), and topoi (P=.045). PINP and PIIINP are useful markers for severe ILD+SSc, suggesting they could play a role in the follow-up of this complication in SSc. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  9. Interstitial radiotherapy

    International Nuclear Information System (INIS)

    Scardino, P.T.; Bretas, F.

    1987-01-01

    The authors now have 20 years of experience with modern techniques of brachytherapy. The large number of patients treated in medical centers around the world and the widespread use of this type of radiotherapy have provided us with substantial information about the indications and contraindications, advantages and disadvantages, pitfalls and complications, as well as the results of these techniques. Although the focus of this review is the experience at Baylor using the combined technique of gold seed implantation plus external beam irradiation, the alternative forms of brachytherapy will be described and compared. The authors' intention is to provide the busy clinician with a succinct and informative review indicating the status of modern interstitial radiotherapy and describing day-to-day approach and results

  10. Phylogenetic Diversity in Core Region of Hepatitis C Virus Genotype 1a as a Factor Associated with Fibrosis Severity in HIV-1-Coinfected Patients

    Directory of Open Access Journals (Sweden)

    Micaela Parra

    2017-01-01

    Full Text Available High hepatitis C virus (HCV genetic diversity impacts infectivity/pathogenicity, influencing chronic liver disease progression associated with fibrosis degrees and hepatocellular carcinoma. HCV core protein is crucial in cell-growth regulation and host-gene expression. Liver fibrosis is accelerated by unknown mechanisms in human immunodeficiency virus-1- (HIV-1- coinfected individuals. We aimed to study whether well-defined HCV-1a core polymorphisms and genetic heterogeneity are related to fibrosis in a highly homogeneous group of interferon-treated HIV-HCV-coinfected patients. Genetic heterogeneity was weighed by Faith’s phylogenetic diversity (PD, which has been little studied in HCV. Eighteen HCV/HIV-coinfected patients presenting different liver fibrosis stages before anti-HCV treatment-initiation were recruited. Sampling at baseline and during and after treatment was performed up to 72 weeks. At inter/intrahost level, HCV-1a populations were studied using molecular cloning and Sanger sequencing. Over 400 complete HCV-1a core sequences encompassing 573 positions of C were obtained. Amino acid substitutions found previously at positions 70 and 91 of HCV-1b core region were not observed. However, HCV genetic heterogeneity was higher in mild than in severe fibrosis cases. These results suggest a potential utility of PD as a virus-related factor associated with chronic hepatitis C progression. These observations should be reassessed in larger cohorts to corroborate our findings and assess other potential covariates.

  11. Pulmonary fibrosis in rheumatoid arthritis: a review of clinical features and therapy.

    Science.gov (United States)

    Roschmann, R A; Rothenberg, R J

    1987-02-01

    During the past four decades there has been a growing appreciation of the frequency of pulmonary abnormalities associated with RA. Approximately 30% to 40% of patients with RA demonstrate either radiographic or pulmonary function abnormalities indicative of interstitial fibrosis or restrictive lung disease. The severity of pulmonary fibrosis is not associated with rheumatologic symptoms or the duration of the associated RA, nor is there any clear relation to the extraarticular features of RA or serologic findings. Survival rates in patients with coexisting RA and pulmonary fibrosis are similar to those of patients with idiopathic pulmonary fibrosis. However, the spectrum of disease activity is quite variable. The majority of patients with progressive pulmonary symptomatology, when treated with corticosteroids, will have equivocal results. Some patients appear to respond to immunosuppressive or cytotoxic medications. The role of macrophages may be central to the injury to lung. Recent studies suggest a potential treatment role for cyclosporine, which may be able to interrupt lymphocyte-stimulated macrophage activation, and thus, fibroblast-mediated fibrosis in patients with pulmonary interstitial fibrosis. Bronchoalveolar lavage studies may delineate subgroups of patients who are more likely to respond to immunosuppressive agents, especially when treatment is started early.

  12. Idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Noble Paul W

    2008-03-01

    Full Text Available Abstract Idiopathic pulmonary fibrosis (IPF is a non-neoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known provocation. IPF is a rare disease which affects approximately 5 million persons worldwide. The prevalence is estimated to be slightly greater in men (20.2/100,000 than in women (13.2/100,000. The mean age at presentation is 66 years. IPF initially manifests with symptoms of exercise-induced breathless and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones upon physical exam. Clubbing is found in approximately 50% of IPF patients. Cor pulmonale develops in association with end-stage disease. In that case, classic signs of right heart failure may be present. Etiology remains incompletely understood. Some environmental factors may be associated with IPF (cigarette smoking, exposure to silica and livestock. IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP. The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images and a lung biopsy. In the absence of lung biopsy, the diagnosis of IPF can be made by defined clinical criteria that were published in guidelines endorsed by several professional societies. Differential diagnosis includes other idiopathic interstitial pneumonia, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis, forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis and other environmental (sometimes occupational exposures. IPF is typically progressive and leads to significant

  13. Interstitial Cells of Blood Vessels

    Directory of Open Access Journals (Sweden)

    Vladimír Pucovský

    2010-01-01

    Full Text Available Blood vessels are made up of several distinct cell types. Although it was originally thought that the tunica media of blood vessels was composed of a homogeneous population of fully differentiated smooth muscle cells, more recent data suggest the existence of multiple smooth muscle cell subpopulations in the vascular wall. One of the cell types contributing to this heterogeneity is the novel, irregularly shaped, noncontractile cell with thin processes, termed interstitial cell, found in the tunica media of both veins and arteries. While the principal role of interstitial cells in veins seems to be pacemaking, the role of arterial interstitial cells is less clear. This review summarises the knowledge of the functional and structural properties of vascular interstitial cells accumulated so far, offers hypotheses on their physiological role, and proposes directions for future research.

  14. Chronic interstitial pneumonia with honeycombing in coal workers

    Energy Technology Data Exchange (ETDEWEB)

    Brichet, A.; Tonnel, A.B.; Brambilla, E.; Devouassoux, G.; Remy-Jardin, M.; Copin, M.C.; Wallaert, B. [A. Calmette Hospital, Lille (France)

    2002-10-01

    Coal worker's pneumoconiosis (CWP) results from coal mine dust inhalation. The paper reports the presence of a chronic interstitial pneumonia (CIP) with honeycombing in 38 cases of coal miners, with or without CWP. The 38 patients were selected on the basis of clinical criteria which are unusual in CWP, i.e. fine inspiratory crackles and severe dyspnea. There were 37 men and one woman; mean age was 67.5 {+-} 9.1 years. Thirty-two were smokers. Duration of exposure was 26.7 {+-} 9.9 years. All the patients had clinical examination, chest radiography, computed tomography (CT), lung function, laboratory investigations, wedged fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). In eight cases, lung specimens were obtained. Seventeen out of 38 had finger clubbing. 17 had radiological signs of CWP limited to the upper lobes or diffusely distributed. CT showed honeycombing (36 cases), and/or ground glass opacities (30 cases) with traction bronchiectasis (8 cases) predominant in the lower lobes. BAL analysis demonstrated an increased percentage of neutrophils (9.4% {+-} 6). Lung function showed a restrictive pattern associated with a decreased DLCO and hypoxemia. Lung specimens demonstrated in 2 cases a homogenous interstitial fibrosis of intra-alveolar septum with an accumulation of immune and inflammatory cells without temporal variation and with obvious honeycombing. The 6 other cases showed features of usual interstitial pneumonia. These cases, should alert other clinicians to a possible association between CIP with honeycombing and coal dust exposure, with or without associated CWP.

  15. A new model of progressive pulmonary fibrosis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. (Univ. of California, Davis (United States))

    1993-08-01

    Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-11-15

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

  18. Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

    Science.gov (United States)

    Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

    2016-01-01

    The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. © The Author(s) 2015.

  19. Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    DePianto, Daryle J; Chandriani, Sanjay; Abbas, Alexander R; Jia, Guiquan; N'Diaye, Elsa N; Caplazi, Patrick; Kauder, Steven E; Biswas, Sabyasachi; Karnik, Satyajit K; Ha, Connie; Modrusan, Zora; Matthay, Michael A; Kukreja, Jasleen; Collard, Harold R; Egen, Jackson G; Wolters, Paul J; Arron, Joseph R

    2015-01-01

    There is microscopic spatial and temporal heterogeneity of pathological changes in idiopathic pulmonary fibrosis (IPF) lung tissue, which may relate to heterogeneity in pathophysiological mediators of disease and clinical progression. We assessed relationships between gene expression patterns, pathological features, and systemic biomarkers to identify biomarkers that reflect the aggregate disease burden in patients with IPF. Gene expression microarrays (N=40 IPF; 8 controls) and immunohistochemical analyses (N=22 IPF; 8 controls) of lung biopsies. Clinical characterisation and blood biomarker levels of MMP3 and CXCL13 in a separate cohort of patients with IPF (N=80). 2940 genes were significantly differentially expressed between IPF and control samples (|fold change| >1.5, p<0.05). Two clusters of co-regulated genes related to bronchiolar epithelium or lymphoid aggregates exhibited substantial heterogeneity within the IPF population. Gene expression in bronchiolar and lymphoid clusters corresponded to the extent of bronchiolisation and lymphoid aggregates determined by immunohistochemistry in adjacent tissue sections. Elevated serum levels of MMP3, encoded in the bronchiolar cluster, and CXCL13, encoded in the lymphoid cluster, corresponded to disease severity and shortened survival time (p<10(-7) for MMP3 and p<10(-5) for CXCL13; Cox proportional hazards model). Microscopic pathological heterogeneity in IPF lung tissue corresponds to specific gene expression patterns related to bronchiolisation and lymphoid aggregates. MMP3 and CXCL13 are systemic biomarkers that reflect the aggregate burden of these pathological features across total lung tissue. These biomarkers may have clinical utility as prognostic and/or surrogate biomarkers of disease activity in interventional studies in IPF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2011-06-01

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

  1. Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

    Science.gov (United States)

    Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua

    2018-06-01

    Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  2. Comparative study of two models of combined pulmonary fibrosis and emphysema in mice.

    Science.gov (United States)

    Zhang, Wan-Guang; Wu, Si-Si; He, Li; Yang, Qun; Feng, Yi-Kuan; Chen, Yue-Tao; Zhen, Guo-Hua; Xu, Yong-Jian; Zhang, Zhen-Xiang; Zhao, Jian-Ping; Zhang, Hui-Lan

    2017-04-01

    Combined pulmonary fibrosis and emphysema (CPFE) is an "umbrella term" encompassing emphysema and pulmonary fibrosis, but its pathogenesis is not known. We established two models of CPFE in mice using tracheal instillation with bleomycin (BLM) or murine gammaherpesvirus 68 (MHV-68). Experimental mice were divided randomly into four groups: A (normal control, n=6), B (emphysema, n=6), C (emphysema+MHV-68, n=24), D (emphysema+BLM, n=6). Group C was subdivided into four groups: C1 (sacrificed on day 367, 7 days after tracheal instillation of MHV-68); C2 (day 374; 14days); C3 (day 381; 21days); C4 (day 388; 28days). Conspicuous emphysema and interstitial fibrosis were observed in BLM and MHV-68 CPFE mouse models. However, BLM induced diffuse pulmonary interstitial fibrosis with severely diffuse pulmonary inflammation; MHV-68 induced relatively modest inflammation and fibrosis, and the inflammation and fibrosis were not diffuse, but instead around bronchioles. Inflammation and fibrosis were detectable in the day-7 subgroup and reached a peak in the day-28 subgroup in the emphysema + MHV-68 group. Levels of macrophage chemoattractant protein-1, macrophage inflammatory protein-1α, interleukin-13, and transforming growth factor-β1 in bronchoalveolar lavage fluid were increased significantly in both models. Percentage of apoptotic type-2 lung epithelial cells was significantly higher; however, all four types of cytokine and number of macrophages were significantly lower in the emphysema+MHV-68 group compared with the emphysema +BLM group. The different changes in pathology between BLM and MHV-68 mice models demonstrated different pathology subtypes of CPFE: macrophage infiltration and apoptosis of type-II lung epithelial cells increased with increasing pathology score for pulmonary fibrosis. Copyright © 2017 Elsevier GmbH. All rights reserved.

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

    Science.gov (United States)

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

    2018-01-01

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

  4. Idiopathic pulmonary fibrosis in a Staffordshire bull terrier with hypothyroidism.

    Science.gov (United States)

    Corcoran, B M; Dukes-McEwan, J; Rhind, S; French, A

    1999-04-01

    Radiographic evidence of chronic interstitial lung changes, usually believed to be attributable to lung fibrosis, is readily recognised in canine practice. Furthermore, there is a body of anecdotal evidence suggesting that a specific clinical entity consistent with chronic lung fibrosis occurs in specific breeds of terrier dogs. However, there is little pathological data to confirm these radiographic and clinical findings and, therefore, chronic interstitial lung disease of dogs is poorly characterised. In this report, a case of chronic pulmonary fibrosis is described in which histopathological confirmation was possible, and suggested that the condition might be analogous to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in humans.

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

    Directory of Open Access Journals (Sweden)

    E.R. Parra

    2012-07-01

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

  6. Changes of bronchoalveolar cell pattern and lecithin content in experimental interstitial pneumonia

    International Nuclear Information System (INIS)

    Manabe, Hideki; Yasuoka, Susumu; Tsubura, Eiro

    1978-01-01

    The pathogenesis of diffuse interstitial fibrosing pneumonitis (DIFP) was studied by histological observations and analysis of the cells and lecithin content of bronchoalveolar lavage of rats with cyclophosphamide (CY)-induced pneumonitis or irradiation pneumonitis. The rats developed diffuse interstitial pneumonitis one week after the last of 5 intraperitoneal injections of 50 mg/kg of CY and gradually recovered in the next 14 weeks. The number of alveolar macrophages and the lecithin content in the bronchoalveolar lavage from these rats corresponded to the degree of inflammatory change of the lung tissue. The results of cell counts and analysis of the bronchoalveolar lavage from rats with irradiated pneumonitis were similar to those on rats with CY-induced pneumonitis, except that in irradiated rats the lecithin content of the lavage decreased with increase in severity of pulmonary fibrosis. These results indicate that the cell number and lecithin content of bronchoalveolar lavage are good parameters for use in diagnosis of DIFP. (auth.)

  7. [Nonspecific interstitial pneumonitis: a clinicopathologic entity, histologic pattern or unclassified group of heterogeneous interstitial pneumonitis?].

    Science.gov (United States)

    Morais, António; Moura, M Conceição Souto; Cruz, M Rosa; Gomes, Isabel

    2004-01-01

    Nonspecific interstitial pneumonitis (NSIP) initially described by Katzenstein and Fiorelli in 1994, seems to be a distinct clinicopathologic entity among idiopathic interstitial pneumonitis (IIP). Besides different histologic features from other IIP, NSIP is characterized by a better long-term outcome, associated with a better steroids responsiveness than idiopathic pulmonar fibrosis (IPF), where usually were included. Thus, differentiating NSIP from other IIP, namely IPF is very significant, since it has important therapeutic and prognostic implications. NSIP encloses different pathologies, namely those with inflammatory predominance (cellular subtype) or fibrous predominance (fibrosing subtype). NSIP is reviewed and discussed by the authors, after two clinical cases description.

  8. Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment

    OpenAIRE

    Khalil, Nasreen; O'Connor, Robert

    2004-01-01

    IDIOPATHIC PULMONARY FIBROSIS (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial pneumonia and are characterized by histological temporal heterogeneity, whereby normal lung tissue is interspersed with interstitial fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show restricted volumes and capacities, preserved flows and evidence of decreased gas exchange. High-resolution computed axial tomogra...

  9. Smoking and Pulmonary Fibrosis: Novel Insights

    Directory of Open Access Journals (Sweden)

    Katerina D. Samara

    2011-01-01

    Full Text Available The relationship between smoking and pulmonary fibrosis is under debate and intense investigation. The aim of this paper is to review the existing literature and identify further areas of research interest. Recently the negative influence of cigarette smoking on IPF outcome was highlighted, as non-smokers exhibit a better survival than ex-smokers and combined current- and ex-smokers. In patients with non-specific interstitial pneumonia (NSIP, a high prevalence of emphysema was recently demonstrated, providing an indirect support for a smoking pathogenetic hypothesis in NSIP. The coexistence of pulmonary fibrosis and emphysema has been extensively described in a syndrome termed combined pulmonary fibrosis and emphysema (CPFE. Connective tissue disorders (CTDs are a group of autoimmune diseases which affect the lung, as one of the most common and severe manifestations. However, the relationship between smoking and autoimmune disorders is still conflicting. Rheumatoid arthritis results from the interaction between genetic and environmental factors, while the best established environmental factor is tobacco smoking. Smoking has also a negative impact on the response of the RA patients to treatment. The aforementioned smoking-related implications give rise to further research questions and certainly provide one more important reason for physicians to advocate smoking cessation and smoke-free environment.

  10. Diagnostic Performance of MR Elastography and Vibration-controlled Transient Elastography in the Detection of Hepatic Fibrosis in Patients with Severe to Morbid Obesity.

    Science.gov (United States)

    Chen, Jun; Yin, Meng; Talwalkar, Jayant A; Oudry, Jennifer; Glaser, Kevin J; Smyrk, Thomas C; Miette, Véronique; Sandrin, Laurent; Ehman, Richard L

    2017-05-01

    Purpose To evaluate the diagnostic performance and examination success rate of magnetic resonance (MR) elastography and vibration-controlled transient elastography (VCTE) in the detection of hepatic fibrosis in patients with severe to morbid obesity. Materials and Methods This prospective and HIPAA-compliant study was approved by the institutional review board. A total of 111 patients (71 women, 40 men) participated. Written informed consent was obtained from all patients. Patients underwent MR elastography with two readers and VCTE with three observers to acquire liver stiffness measurements for liver fibrosis assessment. The results were compared with those from liver biopsy. Each pathology specimen was evaluated by two hepatopathologists according to the METAVIR scoring system or Brunt classification when appropriate. All imaging observers were blinded to the biopsy results, and all hepatopathologists were blinded to the imaging results. Examination success rate, interobserver agreement, and diagnostic accuracy for fibrosis detection were assessed. Results In this obese patient population (mean body mass index = 40.3 kg/m 2 ; 95% confidence interval [CI]: 38.7 kg/m 2 , 41.8 kg/m 2 ]), the examination success rate was 95.8% (92 of 96 patients) for MR elastography and 81.3% (78 of 96 patients) or 88.5% (85 of 96 patients) for VCTE. Interobserver agreement was higher with MR elastography than with biopsy (intraclass correlation coefficient, 0.95 vs 0.89). In patients with successful MR elastography and VCTE examinations (excluding unreliable VCTE examinations), both MR elastography and VCTE had excellent diagnostic accuracy in the detection of clinically significant hepatic fibrosis (stage F2-F4) (mean area under the curve: 0.93 [95% CI: 0.85, 0.97] vs 0.91 [95% CI: 0.83, 0.96]; P = .551). Conclusion In this obese patient population, both MR elastography and VCTE had excellent diagnostic performance for assessing hepatic fibrosis; MR elastography was more

  11. HRCT appearances of pulmonary interstitial diseases. The pathologic basis and clinical diagnostic significance

    International Nuclear Information System (INIS)

    Ma Daqing; Li Tieyi; Guan Yansheng; He Wen; Nie Yongkang

    1999-01-01

    Objective: To evaluate the CT appearances, the pathologic basis and diagnostic significance of pulmonary interstitial diseases. methods: 14 isolated lungs with interstitial diseases were obtained at autopsy and surgery. The lungs were inflated and fixed. HRCT and 1 cm thin slice soft X-ray radiograph were performed and then histologic examination was done. HRCT images of 72 cases with interstitial diseases were analysed. The HRCT appearances of 10 cases were followed up for 1.5-7.0 years. Results: According to HRCT-pathologic correlation, pulmonary interstitial diseases had the following HRCT findings: (1) Intralobular interstitial thickening (33 cases, 46%), including fine linear, reticular and radiating appearances and the interface sign. (2) Interlobular septal thickening (24 cases, 33%). (3) Thickening of bronchovesicular bundles (35 cases, 49%), with coarse, blurred or smooth bundle, and nodular shape. (4) Subpleural lines (31 cases, 43%). (5) Ground-glass opacity (22 cases, 31%) with peripheral, diffuse or locular distribution. (6) Honeycombing (27 cases, 38%), having sizes: 5 mm. Of the 10 cases with follow-up, 2 cases became normal on CT and 8 cases progressing to honeycombed lung. Conclusions: The HRCT findings of pulmonary interstitial diseases represent abnormalities of axial, peripheral and septal interstitium. Interstitial fibrosis of the lung can be differentiated from that without fibrosis by HRCT. Ground-glass opacity, intralobular interstitial thickening and subpleural lines are preliminary findings of pulmonary interstitial fibrosis

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

    Science.gov (United States)

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

    2008-01-01

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

  13. Introduction to Pulmonary Fibrosis

    Science.gov (United States)

    ... page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is a disease where there is scarring ... of pulmonary fibrosis. Learn more How Is Pulmonary Fibrosis Diagnosed? Pulmonary fibrosis can be difficult to diagnose, so it ...

  14. Functional and prognostic effects when emphysema complicates idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Jacob, Joseph; Bartholmai, Brian J; Rajagopalan, Srinivasan; Kokosi, Maria; Maher, Toby M; Nair, Arjun; Karwoski, Ronald; Renzoni, Elisabetta; Walsh, Simon L F; Hansell, David M; Wells, Athol U

    2017-07-01

    This study aimed to investigate whether the combination of fibrosis and emphysema has a greater effect than the sum of its parts on functional indices and outcome in idiopathic pulmonary fibrosis (IPF), using visual and computer-based (CALIPER) computed tomography (CT) analysis.Consecutive patients (n=272) with a multidisciplinary IPF diagnosis had the extent of interstitial lung disease (ILD) scored visually and by CALIPER. Visually scored emphysema was subcategorised as isolated or mixed with fibrotic lung. The CT scores were evaluated against functional indices forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide ( D LCO ), transfer coefficient of the lung for carbon monoxide ( K CO ), composite physiologic index (CPI)) and mortality.The presence and extent of emphysema had no impact on survival. Results were maintained following correction for age, gender, smoking status and baseline severity using D LCO , and combined visual emphysema and ILD extent. Visual emphysema quantitation indicated that relative preservation of lung volumes (FVC) resulted from tractionally dilated airways within fibrotic lung, ventilating areas of admixed emphysema (pemphysema. Conversely, only isolated emphysema (pemphysema in IPF, beyond that explained by the additive extents of both fibrosis and emphysema. With respect to the location of pulmonary fibrosis, emphysema distribution determines the functional effects of emphysema. Copyright ©ERS 2017.

  15. Genetics and Early Detection in Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Putman, Rachel K.; Rosas, Ivan O.

    2014-01-01

    Genetic studies hold promise in helping to identify patients with early idiopathic pulmonary fibrosis (IPF). Recent studies using chest computed tomograms (CTs) in smokers and in the general population have demonstrated that imaging abnormalities suggestive of an early stage of pulmonary fibrosis are not uncommon and are associated with respiratory symptoms, physical examination abnormalities, and physiologic decrements expected, but less severe than those noted in patients with IPF. Similarly, recent genetic studies have demonstrated strong and replicable associations between a common promoter polymorphism in the mucin 5B gene (MUC5B) and both IPF and the presence of abnormal imaging findings in the general population. Despite these findings, it is important to note that the definition of early-stage IPF remains unclear, limited data exist to definitively connect abnormal imaging findings to IPF, and genetic studies assessing early-stage pulmonary fibrosis remain in their infancy. In this perspective we provide updated information on interstitial lung abnormalities and their connection to IPF. We summarize information on the genetics of pulmonary fibrosis by focusing on the recent genetic findings of MUC5B. Finally, we discuss the implications of these findings and suggest a roadmap for the use of genetics in the detection of early IPF. PMID:24547893

  16. Idiopathic pulmonary fibrosis: treatment update.

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2011-11-01

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

  17. Hypothalamic digoxin, hemispheric chemical dominance, and interstitial lung disease.

    Science.gov (United States)

    Kurup, Ravi Kumar; Kurup, Parameswara Achutha

    2003-10-01

    The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with idiopathic pulmonary fibrosis and in individuals of differing hemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of idiopathic pulmonary fibrosis. All 15 cases of interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. The isoprenoidal metabolites--digoxin, dolichol, and ubiquinone, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, tyrosine/tryptophan catabolic patterns, free radical metabolism, glycoconjugate metabolism, and RBC membrane composition--were assessed in idiopathic pulmonary fibrosis as well as in individuals with differing hemispheric dominance. In patients with idiopathic pulmonary fibrosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in patients with idiopathic pulmonary fibrosis. Isoprenoid pathway dysfunction con tributes to the pathogenesis of idiopathic pulmonary fibrosis. The biochemical patterns obtained in interstitial lung disease are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. However, all the patients with interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Interstitial lung disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

  18. Radionuclide study for the interstitial lung disease

    International Nuclear Information System (INIS)

    Kawakami, Kenji; Mori, Yutaka; Ujita, Masuo

    1991-01-01

    The contribution of pulmonary nuclear medicine was evaluated in 105 patients with interstitial pulmonary diseases (IPD). Ventilation study (V) with 81m Kr, distribution of compliance in thoraco-pulmonary system (C) by 81m Kr gas bolus inhalation method, perfusion study (Q) with 99m Tc-MAA, 67 Ga scintigraphy and an assessment of pulmonary epithelial permeability with 99m Tc-DTPA aerosol were performed as nuclear medicine procedures. Pulmonary function test (%DLco, vital capacity and functional residual capacity) and blood gas analysis were also examined. Abnormalities in V were larger than that in Q which was high V/Q mismatch finding, in the interstitial pneumonia. Correlation between V/Q mismatch and PaO 2 was, therefore, not significant. %DLco was decreased in cases with larger V/Q mismatches. 67 Ga accumulated in the early stage of interstitial pneumonia when CT or chest X-ray did not show any finding. %DLco was decreased in cases with strong accumulation of 67 Ga. 67 Ga might be useful to evaluate activity of the diseases. Pulmonary epithelial permeability was assessed by 99m Tc-DTPA inhalation study. This permeability accelerated in idiopathic interstitial fibrosis and sarcoidosis. Pulmonary epithelial permeability may be useful as an indicator for epithelial cell injury. (author)

  19. Radionuclide study for the interstitial lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Kenji; Mori, Yutaka; Ujita, Masuo (Jikei Univ., Tokyo (Japan). School of Medicine)

    1991-07-01

    The contribution of pulmonary nuclear medicine was evaluated in 105 patients with interstitial pulmonary diseases (IPD). Ventilation study (V) with {sup 81m}Kr, distribution of compliance in thoraco-pulmonary system (C) by {sup 81m}Kr gas bolus inhalation method, perfusion study (Q) with {sup 99m}Tc-MAA, {sup 67}Ga scintigraphy and an assessment of pulmonary epithelial permeability with {sup 99m}Tc-DTPA aerosol were performed as nuclear medicine procedures. Pulmonary function test (%DLco, vital capacity and functional residual capacity) and blood gas analysis were also examined. Abnormalities in V were larger than that in Q which was high V/Q mismatch finding, in the interstitial pneumonia. Correlation between V/Q mismatch and PaO{sub 2} was, therefore, not significant. %DLco was decreased in cases with larger V/Q mismatches. {sup 67}Ga accumulated in the early stage of interstitial pneumonia when CT or chest X-ray did not show any finding. %DLco was decreased in cases with strong accumulation of {sup 67}Ga. {sup 67}Ga might be useful to evaluate activity of the diseases. Pulmonary epithelial permeability was assessed by {sup 99m}Tc-DTPA inhalation study. This permeability accelerated in idiopathic interstitial fibrosis and sarcoidosis. Pulmonary epithelial permeability may be useful as an indicator for epithelial cell injury. (author).

  20. Disease activity of idiopathic pulmonary fibrosis -value of high resolution CT-

    International Nuclear Information System (INIS)

    Lee, Jin Seong; Im, Jung Gi; Han, Man Chung; Kim, Chu Wan; Suh, Jin Suk

    1991-01-01

    Idiopathic pulmonary fibrosis (IPF) has characteristic clinical and pathologic features. In patients with uniform intra-alveolar cellularity, the process is often referred to as desquamative interstitial pneumonia. When alveolar septal fibrosis predominate, the process is known as usual interstitial pneumonia. Recently most investigators believe that desquamative interstitial pneumonia is the early stage and usual interstitial pneumonia is the late stage of the same disease process. The lone-term survival and the best response to treatment with corticosteroids is found in patients with marked disease activity and little fibrosis. Since disease activity is reflected by interstitial and intraalveolar cellularity, activity of idiopathic pulmonary fibrosis might result in opacification of air spaces on CT scans. There was no significant difference in estimating the visual HRCT scores of active area between two observers (p>0.05). Activity score of HRCT scan correlated significantly with improvement of DLCO/VA after corticosteroids treatment

  1. Disease activity of idiopathic pulmonary fibrosis -value of high resolution CT-

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin Seong; Im, Jung Gi; Han, Man Chung; Kim, Chu Wan; Suh, Jin Suk [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1991-01-15

    Idiopathic pulmonary fibrosis (IPF) has characteristic clinical and pathologic features. In patients with uniform intra-alveolar cellularity, the process is often referred to as desquamative interstitial pneumonia. When alveolar septal fibrosis predominate, the process is known as usual interstitial pneumonia. Recently most investigators believe that desquamative interstitial pneumonia is the early stage and usual interstitial pneumonia is the late stage of the same disease process. The lone-term survival and the best response to treatment with corticosteroids is found in patients with marked disease activity and little fibrosis. Since disease activity is reflected by interstitial and intraalveolar cellularity, activity of idiopathic pulmonary fibrosis might result in opacification of air spaces on CT scans. There was no significant difference in estimating the visual HRCT scores of active area between two observers (p>0.05). Activity score of HRCT scan correlated significantly with improvement of DLCO/VA after corticosteroids treatment.

  2. Subclinical interstitial lung involvement in rheumatic diseases. Correlations of high-resolution Computed Tomography patterns with functional and cytologic findings

    International Nuclear Information System (INIS)

    Salaffi, F.; Baldelli, S.

    1999-01-01

    The aims of this study were to quantify the severity and extent of subclinical interstitial lung disease as depicted on HRCT and to study the relationship between the patterns of lung disease quantified by HRCT and the functional parameters and bronchoalveolar lavage findings in patients with rheumatic diseases. The results confirm that HRCT is a sensitive tool in detecting interstitial lung disease in patients with rheumatic diseases with no signs and symptoms of pulmonary involvement. The relationship between the different HRCT patterns and bronchoalveolar lavage cell profiles can identify patients at higher risk of developing irreversible lung fibrosis. A long-term, prospective follow-up study is needed to determine whether these patients will develop over pulmonary disease [it

  3. Acute interstitial pneumonia

    International Nuclear Information System (INIS)

    Cuervo M, Francisco; Carrillo Bayona, Jorge; Ojeda, Paulina

    2004-01-01

    The paper refers to a 71 year-old patient, to who is diagnosed acute interstitial pneumonia; with square of 20 days of evolution of cough dry emetizant, fever, general uneasiness, migraine, progressive dyspnoea and lost of weight

  4. Intracranial interstitial radiation

    International Nuclear Information System (INIS)

    Willis, D.; Rittenmeyer, H.; Hitchon, P.

    1986-01-01

    Primary malignant brain tumors are fatal, with 90% of patients having these tumors dying within two years following diagnosis. Cranial interstitial radiation therapy, a technique under investigation to control these tumors, involves implantation of radioactive iodine 125 seeds into the tumor bed by stereotaxic technique. The interstitial radiation technique, monitoring of radiation, and nursing care of patients are discussed. Case histories are presented, along with discussion of results attained using this therapy, and its future

  5. Smoking-related interstitial lung diseases: radiologic-pathologic correlation

    International Nuclear Information System (INIS)

    Hidalgo, Alberto; Franquet, Tomas; Gimenez, Ana; Pineda, Rosa; Madrid, Marta; Bordes, Ramon

    2006-01-01

    Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis. (orig.)

  6. Smoking-related interstitial lung diseases: radiologic-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Hidalgo, Alberto [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Hospital de la Santa Creu i Sant Pau, Thoracic Radiology, Department of Radiology, Barcelona (Spain); Franquet, Tomas; Gimenez, Ana; Pineda, Rosa; Madrid, Marta [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Bordes, Ramon [Universidad Autonoma de Barcelona, Department of Pathology, Hospital de Sant Pau, Barcelona (Spain)

    2006-11-15

    Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis. (orig.)

  7. Protein S is protective in pulmonary fibrosis.

    Science.gov (United States)

    Urawa, M; Kobayashi, T; D'Alessandro-Gabazza, C N; Fujimoto, H; Toda, M; Roeen, Z; Hinneh, J A; Yasuma, T; Takei, Y; Taguchi, O; Gabazza, E C

    2016-08-01

    Essentials Epithelial cell apoptosis is critical in the pathogenesis of idiopathic pulmonary fibrosis. Protein S, a circulating anticoagulant, inhibited apoptosis of lung epithelial cells. Overexpression of protein S in lung cells reduced bleomycin-induced pulmonary fibrosis. Intranasal therapy with exogenous protein S ameliorated bleomycin-induced pulmonary fibrosis. Background Pulmonary fibrosis is the terminal stage of interstitial lung diseases, some of them being incurable and of unknown etiology. Apoptosis plays a critical role in lung fibrogenesis. Protein S is a plasma anticoagulant with potent antiapoptotic activity. The role of protein S in pulmonary fibrosis is unknown. Objectives To evaluate the clinical relevance of protein S and its protective role in pulmonary fibrosis. Methods and Results The circulating level of protein S was measured in patients with pulmonary fibrosis and controls by the use of enzyme immunoassays. Pulmonary fibrosis was induced with bleomycin in transgenic mice overexpressing human protein S and wild-type mice, and exogenous protein S or vehicle was administered to wild-type mice; fibrosis was then compared in both models. Patients with pulmonary fibrosis had reduced circulating levels of protein S as compared with controls. Inflammatory changes, the levels of profibrotic cytokines, fibrosis score, hydroxyproline content in the lungs and oxygen desaturation were significantly reduced in protein S-transgenic mice as compared with wild-type mice. Wild-type mice treated with exogenous protein S showed significant decreases in the levels of inflammatory and profibrotic markers and fibrosis in the lungs as compared with untreated control mice. After bleomycin infusion, mice overexpressing human protein S showed significantly low caspase-3 activity, enhanced expression of antiapoptotic molecules and enhanced Akt and Axl kinase phosphorylation as compared with wild-type counterparts. Protein S also inhibited apoptosis of alveolar

  8. Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Takafumi Suda

    2015-01-01

    Full Text Available Pulmonary involvement is common in rheumatoid arthritis (RA and affects all the components of the lung. Interstitial lung disease (ILD is the most predominant pulmonary manifestation and has been identified as the main cause of morbidity and mortality in RA. Clinically significant RA-ILD occurs in approximately 10% of RA patients. Several risk factors, such as old age, male gender, and smoking, have been reported to date. Histologically, the proportion of the usual interstitial pneumonia (UIP pattern is higher in RA-ILD than in ILD associated with other connective tissue diseases, and RA-ILD also shows nonspecific interstitial pneumonia and organizing pneumonia patterns. High-resolution computed tomography scans are highly predictive of the histological UIP pattern with a specificity of 96%-100%. Acute exacerbation, which is the acute deterioration of the respiratory status characterized by newly developed bilateral infiltrates with unknown etiologies, has been reported in RA-ILD. Although acute exacerbation of RA-ILD has high mortality, similar to that of idiopathic pulmonary fibrosis, its incidence is lower in RA-ILD than in idiopathic pulmonary fibrosis. A consensus treatment has not yet been established. Current therapeutic regimens typically include corticosteroids with or without cytotoxic agents. Recent large longitudinal studies reported that the prognosis of RA-ILD was poor with a median survival of 2.6-3.0 years. Furthermore, histological and/or radiological patterns, such as UIP or non-UIP, have significant prognostic implications. RA-ILD patients with histological or radiological UIP patterns have poorer prognoses than those with non-UIP patterns. This review assessed the characteristics of RA-ILD by overviewing recent studies in the field and focused on the clinical significance of histological and/or radiological patterns in RA-ILD.

  9. Further characterization of computed tomographic and clinical features for staging and prognosis of idiopathic pulmonary fibrosis in West Highland white terriers.

    Science.gov (United States)

    Thierry, Florence; Handel, Ian; Hammond, Gawain; King, Lesley G; Corcoran, Brendan M; Schwarz, Tobias

    2017-07-01

    Idiopathic pulmonary fibrosis is an interstitial lung disease of unknown etiology resulting in progressive interstitial fibrosis, with a known predilection in West Highland white terriers. In humans, computed tomography (CT) is a standard method for providing diagnostic and prognostic information, and plays a major role in the idiopathic pulmonary fibrosis staging process. Objectives of this retrospective, analytical, cross-sectional study were to establish descriptive criteria for reporting CT findings and test correlations among CT, clinical findings and survival time in West Highland white terriers with idiopathic pulmonary fibrosis. Inclusion criteria for affected West Highland white terriers were a diagnosis of idiopathic pulmonary fibrosis and available CT, bronchoscopy, bronchoalveolar lavage, echocardiography, and routine blood analysis findings. Clinically normal West Highland white terriers were recruited for the control group. Survival times were recorded for affected dogs. The main CT lung pattern and clinical data were blindly and separately graded as mild, moderate, or severe. Twenty-one West Highland white terriers with idiopathic pulmonary fibrosis and 11 control West Highland white terriers were included. The severity of pulmonary CT findings was positively correlated with severity of clinical signs (ρ = 0.48, P = 0.029) and negatively associated with survival time after diagnosis (ρ = -0.56, P = 0.025). Affected dogs had higher lung attenuation (median: -563 Hounsfield Units (HU)) than control dogs (median: -761 HU), (P idiopathic pulmonary fibrosis in West Highland white terriers and providing prognostic information for owners. © 2017 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Radiology.

  10. A composite model including visfatin, tissue polypeptide-specific antigen, hyaluronic acid, and hematological variables for the diagnosis of moderate-to-severe fibrosis in nonalcoholic fatty liver disease: a preliminary study.

    Science.gov (United States)

    Chwist, Alina; Hartleb, Marek; Lekstan, Andrzej; Kukla, Michał; Gutkowski, Krzysztof; Kajor, Maciej

    2014-01-01

    Histopathological risk factors for end-stage liver failure in patients with nonalcoholic fatty liver disease (NAFLD) include nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis. There is a need for noninvasive diagnostic methods for these 2 conditions. The aim of this study was to investigate new laboratory variables with a predictive potential to detect advanced fibrosis (stages 2 and 3) in NAFLD. The study involved 70 patients with histologically proven NAFLD of varied severity. Additional laboratory variables included zonulin, haptoglobin, visfatin, adiponectin, leptin, tissue polypeptide-specific antigen (TPSA), hyaluronic acid, and interleukin 6. Patients with NASH (NAFLD activity score of ≥5) had significantly higher HOMA-IR values and serum levels of visfatin, haptoglobin, and zonulin as compared with those without NASH on histological examination. Advanced fibrosis was found in 16 patients (22.9%) and the risk factors associated with its prevalence were age, the ratio of erythrocyte count to red blood cell distribution width, platelet count, and serum levels of visfatin and TPSA. Based on these variables, we constructed a scoring system that differentiated between NAFLD patients with and without advanced fibrosis with a sensitivity of 75% and specificity of 100% (area under the receiver operating characteristic curve, 0.93). The scoring system based on the above variables allows to predict advanced fibrosis with high sensitivity and specificity. However, its clinical utility should be verified in further studies involving a larger number of patients.

  11. Forma acelerada da fibrose pulmonar idiopática no pulmão nativo após transplante pulmonar unilateral Accelerated form of interstitial pulmonary fibrosis in the native lung after single lung transplantation

    Directory of Open Access Journals (Sweden)

    Rogério Rufino

    2007-12-01

    Full Text Available Relatamos o caso de um paciente de 56 anos submetido a transplante pulmonar unilateral esquerdo em decorrência de fibrose pulmonar idiopática (FPI. No pós-operatório imediato, sob intensa imunossupressão, houve progressão rápida da FPI no pulmão nativo direito, confirmada pela biópsia pulmonar videotoracoscópica, necessitando de ventilação mecânica durante 104 dias até a realização de outro transplante pulmonar à direita. Obteve alta hospitalar após o 26º dia do segundo pós-operatório.We report the case of a 56-year-old patient who underwent left single lung transplantation for idiopathic pulmonary fibrosis (IPF. Despite the high level of immunosuppression after the surgery, there was rapid progression to IPF in the native (right lung as demonstrated by thoracoscopic lung biopsy. After 104 days on mechanical ventilation (MV, the patient underwent right lung transplant and was discharged from the hospital on postoperative day 26.

  12. Dyskeratosis Congenita Associated Non-Specific Interstitial Pneumonia

    Directory of Open Access Journals (Sweden)

    Unnati D. Desai

    2017-01-01

    Full Text Available Dyskeratosis Congenita (DC is a rare inherited disorder of ectodermal dysplasia. It consists of a classical mucocutaneous triad of abnormal skin pigmentation, nail dystrophy and leukoplakia. Pulmonary disease is seen in 10-15%. It is characterized by Idiopathic Pulmonary Fibrosis (IPF, or Idiopathic Familial Pulmonary Fibrosis (IFPF. Non-specific Interstitial Pneumonia (NSIP has been reported rarely in children with DC and in an isolated adult patient. Our patient had classical clinical presentation of DC with pancytopenia and portal hypertension and clinic-radiological features of NSIP which is a rare association.

  13. Interstitial Lung Disease

    Science.gov (United States)

    ... of Medicine Division of Pulmonary, Critical Care and Sleep Medicine (Adult) Familial Pulmonary Fibrosis (FPF) Genetic Counseling Program Pulmonary Rehabilitation Section of Sleep Medicine Search Directory Our Specialists Kevin K. Brown, MD + × ...

  14. Childhood Interstitial Lung Disease

    Science.gov (United States)

    ... rule out conditions such as asthma , cystic fibrosis , acid reflux, heart disease, neuromuscular disease, and immune deficiency. Various ... a lung infection. Acid-blocking medicines can prevent acid reflux, which can lead to aspiration. Lung Transplant A ...

  15. Interstitial Lung disease in Systemic Sclerosis

    International Nuclear Information System (INIS)

    Ooi, G.C.; Mok, M.Y.; Tsang, K.W.T.; Khong, P.L.; Fung, P.C.W.; Chan, S.; Tse, H.F.; Wong, R.W.S.; Lam, W.K.; Lau, C.S.; Wong, Y.

    2003-01-01

    Purpose: To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. Material and Methods: : 45 SSc patients (40 women, 48.5±13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. Results: ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. Conclusion: Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively

  16. A pilot outreach physiotherapy and dietetic quality improvement initiative reduces IV antibiotic requirements in children with moderate-severe cystic fibrosis.

    Science.gov (United States)

    Ledger, Sean J; Owen, Elizabeth; Prasad, S Ammani; Goldman, Allan; Willams, Jane; Aurora, Paul

    2013-12-01

    At our hospital the current model of care for children with moderate-severe CF is focused on intensive inpatient intervention, regular outpatient clinic review and specialist outreach care as required. An alternative model providing more regular physiotherapy and dietetic outreach support, in addition to these specialist services, may be more effective. 16 children (4 male; 12 female; mean age 10.9±2.93; range 4-15 years) who required >40days of IV antibiotics in the 12-months pre-intervention were enrolled. Physiotherapy included weekly-supervised exercise sessions, alongside regular review of home physiotherapy regimens. Dietetic management included 1-2 monthly monitoring of growth, appetite, intake and absorption, and nutrition education sessions. There was a 23% reduction in inpatient IV antibiotic requirement and 20% reduction in home IV antibiotic requirement during the intervention year. Cost-benefit analyses showed savings of £113,570. VO(2Peak) increased by 4.9 ml·kg·min(-1) (95%CI 1.01 to 8.71; p=0.02), and 10 m-MSWT distance and increment achieved increased by 229 m (95%CI 109 to 350; pchildren with moderate-severe CF. A fully powered clinical trial is now warranted. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  17. Experimental models of liver fibrosis.

    Science.gov (United States)

    Yanguas, Sara Crespo; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2016-05-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

  18. Análise semiquantitativa de biópsias cirúrgicas de diferentes lobos pulmonares de pacientes com pneumonia intersticial usual/fibrose pulmonar idiopática Semiquantitative analysis of surgical biopsies of distinct lung lobes of patients with usual interstitial pneumonia/idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    José Júlio Saraiva Gonçalves

    2009-07-01

    Full Text Available OBJETIVO: Avaliar as diferenças histológicas da pneumonia intersticial usual entre biópsias cirúrgicas de lobos pulmonares distintos, utilizando um escore semiquantitativo. MÉTODOS: Foram selecionados todos os pacientes com o diagnóstico de fibrose pulmonar idiopática e submetidos à biópsia cirúrgica em dois lobos distintos no Hospital São Paulo e em hospitais afiliados da Universidade Federal de São Paulo, no período entre 1995 e 2005. Foi utilizado um método semiquantitativo na avaliação histológica dos espécimes, com base em estudos prévios, aplicando-se um escore para cada local submetido à biópsia. RESULTADOS: Nenhuma diferença estatisticamente significante foi encontrada nesta amostra de pacientes que viesse alterar o estágio da doença, com base no escore utilizado. Este achado foi independente do local da biópsia (lobo médio ou segmento lingular. CONCLUSÕES: Não foram observadas diferenças histológicas significantes entre os lobos pulmonares estudados. O diagnóstico histológico definitivo de pneumonia intersticial usual não alterou o estágio da doença.OBJECTIVE: To evaluate the differences between surgical biopsies of distinct lung lobes in terms of the histopathological features of usual interstitial pneumonia, using a semiquantitative score. METHODS: We selected all of the patients diagnosed with idiopathic pulmonary fibrosis and submitted to surgical biopsy in two distinct lobes between 1995 and 2005 at the Hospital São Paulo and other hospitals operated by the Federal University of São Paulo. In the histological evaluation of the specimens, we used a semiquantitative method based on previous studies, assigning a score to each of the biopsied sites. RESULTS: In this sample of patients, we found no statistically significant differences that would alter the stage of the disease, based on the score used. This finding was independent of the biopsy site (middle lobe or lingular segment. CONCLUSIONS: No

  19. Lung disease severity in idiopathic pulmonary fibrosis is more strongly associated with impedance measures of bolus reflux than pH parameters of acid reflux alone.

    Science.gov (United States)

    Gavini, S; Borges, L F; Finn, R T; Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

    2017-05-01

    Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF). Pathogenesis may be related to chronic micro-aspiration. We aimed to assess objective measures of GER on multichannel intraluminal impedance and pH study (MII-pH) and their relationship with pulmonary function testing (PFT) results, and to compare the performance of pH/acid reflux parameters vs corresponding MII/bolus parameters in predicting pulmonary dysfunction in IPF. This was a retrospective cohort study of IPF patients undergoing prelung transplant evaluation with MII-pH off acid suppression, and having received PFT within 3 months. Patients with prior fundoplication were excluded. Severe pulmonary dysfunction was defined using diffusion capacity of the lung for carbon monoxide (DLCO) ≤40%. Six pH/acid reflux parameters with corresponding MII/bolus reflux measures were specified a priori. Multivariate analyses were applied using forward stepwise logistic regression. Predictive value of each parameter for severe pulmonary dysfunction was calculated by area-under-the-receiver-operating-characteristic-curve or c-statistic. Forty-five subjects (67% M, age 59, 15 mild-moderate vs 30 severe) met criteria for inclusion. Patient demographics and clinical characteristics were similar between pulmonary dysfunction groups. Abnormal total reflux episodes and prolonged bolus clearance time were significantly associated with pulmonary dysfunction severity on univariate and multivariate analyses. No pH parameters were significant. The c-statistic of each pH parameter was lower than its MII counterpart in predicting pulmonary dysfunction. MII/bolus reflux, but not pH/acid reflux, was associated with pulmonary dysfunction in prelung transplant patients with IPF. MII-pH may be more valuable than pH testing alone in characterizing GER in IPF. © 2016 John Wiley & Sons Ltd.

  20. Statin Use Is Associated with Reduced Mortality in Patients with Interstitial Lung Disease

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune F; Nordestgaard, Børge G

    2015-01-01

    INTRODUCTION: We hypothesized that statin use begun before the diagnosis of interstitial lung disease is associated with reduced mortality. METHODS: We studied all patients diagnosed with interstitial lung disease in the entire Danish population from 1995 through 2009, comparing statin use versus...... no statin use in a nested 1:2 matched study. RESULTS: The cumulative survival as a function of follow-up time from the date of diagnosis of interstitial lung disease (n = 1,786 + 3,572) and idiopathic lung fibrosis (n = 261 + 522) was higher for statin users versus never users (log-rank: P = 7 · 10......(-9) and P = 0.05). The median survival time in patients with interstitial lung disease was 3.3 years in statin users and 2.1 years in never users. Corresponding values in patients with idiopathic lung fibrosis were 3.4 versus 2.4 years. After multivariable adjustment, the hazard ratio for all...

  1. The reliability of lung ultrasound in assessment of idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Manolescu D

    2018-03-01

    Full Text Available Diana Manolescu,1 Lavinia Davidescu,2 Daniel Traila,3 Cristian Oancea,3 Voicu Tudorache3 1Radiology Department, University of Medicine and Pharmacy “Victor Babes”, Timişoara, Romania; 2Department of Pulmonology, University of Medicine and Pharmacy Oradea, Oradea, Romania; 3Department of Pulmonology, University of Medicine and Pharmacy “Victor Babes”, Timişoara, Romania Abstract: Idiopathic pulmonary fibrosis (IPF is the severest form of idiopathic interstitial pneumonia, with a median survival time estimated at 2–5 years from the time of diagnosis. It occurs mainly in elderly adults, suggesting a strong link between the fibrosis process and aging. Although chest high-resolution computed tomography (HRCT is currently the method of choice in IPF assessment, diagnostic imaging with typical usual interstitial pneumonia (UIP provides definitive results in only 55%, requiring an invasive surgical procedure such as lung biopsy or cryobiopsy for the final diagnostic analysis. Lung ultrasound (LUS as a noninvasive, non-radiating examination is very sensitive to detect subtle changes in the subpleural space. The evidence of diffuse, multiple B-lines defined as vertical, hyperechoic artifacts is the hallmark of interstitial syndrome. A thick, irregular, fragmented pleura line is associated with subpleural fibrotic scars. The total numbers of B-lines are correlated with the extension of pulmonary fibrosis on HRCT, being an LUS marker of severity. The average distance between two adjacent B-lines is an indicator of a particular pattern on HRCT. It is used to appreciate a pure reticular fibrotic pattern as in IPF compared with a predominant ground glass pattern seen in fibrotic nonspecific interstitial pattern. The distribution of the LUS artifacts has a diagnostic value. An upper predominance of multiple B-lines associated with the thickening of pleura line is an LUS feature of an inconsistent UIP pattern, excluding the IPF diagnosis. LUS is a

  2. Evidence of interstitial microsegregation in iron obtained by ion microscopy

    International Nuclear Information System (INIS)

    Price, C.W.

    1984-01-01

    Segregation of impurity atoms to the strain fields of dislocations and the effective locking of the dislocations by the impurity atmospheres have been suggested earlier by others. The formation of interstitial atmospheres and their effect in iron was first treated mathematically by Cottrell and Bilby (Proc. Phys. Soc.; A62: 49(1949). Hirth and Lothe (Theory of Discolations, McGraw-Hill, New York (1968) reviewed more recent evidence of interstitial effects and theoretical treatments of interstitial dislocation interactions. This paper describes additional evidence of microsegregation of several interstitial elements in iron that were detected using secondary-ion mass spectroscopy (SIMS). 10 references, 2 figures

  3. 67Gallium citrate lung scans in interstitial lung disease

    International Nuclear Information System (INIS)

    Niden, A.H.; Mishkin, F.S.; Khurana, M.M.L.

    1976-01-01

    Patients with diffuse interstitial lung disease often require a lung biopsy to determine the diagnosis and proper therapy. However, once the diagnosis is established, clinical evaluation of symptoms, chest roentgenogram and pulmonary function testing are the only noninvasive means currently available to assess activity of the disease process and response to the therapy. Although these measures appear adequate in the presence of acute active disease in which response to therapy results in readily demonstrable changes in the above parameters, they may be insensitive to subtle changes that can occur in minimally active disease with slowly progressive interstitial pulmonary fibrosis over a period of years. A more sensitive noninvasive technique for identifying these cases with a smoldering diffuse interstitial inflammatory process might greatly improve our ability to effectively manage such patients. With this in mind, the value of gallium lung scan was investigated to assess its ability to predict inflammatory activity in such a clinical setting

  4. /sup 67/Gallium citrate lung scans in interstitial lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Niden, A.H.; Mishkin, F.S.; Khurana, M.M.L.

    1976-02-01

    Patients with diffuse interstitial lung disease often require a lung biopsy to determine the diagnosis and proper therapy. However, once the diagnosis is established, clinical evaluation of symptoms, chest roentgenogram and pulmonary function testing are the only noninvasive means currently available to assess activity of the disease process and response to the therapy. Although these measures appear adequate in the presence of acute active disease in which response to therapy results in readily demonstrable changes in the above parameters, they may be insensitive to subtle changes that can occur in minimally active disease with slowly progressive interstitial pulmonary fibrosis over a period of years. A more sensitive noninvasive technique for identifying these cases with a smoldering diffuse interstitial inflammatory process might greatly improve our ability to effectively manage such patients. With this in mind, the value of gallium lung scan was investigated to assess its ability to predict inflammatory activity in such a clinical setting.

  5. Interstitial irradiation for craniopharyngioma

    International Nuclear Information System (INIS)

    Barlas, O.; Bayindir, C.; Can, M.

    2000-01-01

    The results of interstitial irradiation treatment for craniopharyngioma in two patients with six year follow-ups are presented. Stereotactic interstitial irradiation with iodine-125 sources as sole therapy was employed in two adult patients who refused surgical resection. The diagnoses were confirmed by stereotactic biopsy. The first tumour which underwent interstitial irradiation was solid and 4 cm in diameter, and the second, 2.7 cm in diameter, had both cystic and solid components. The implanted iodine-125 seeds delivered 67 Gy and 60 Gy to tumour periphery at the rate of 12 and 14 cGy/h, respectively, were removed at the end of designated radiation periods. Tumour shrinkage and central hypo density, first observed 3 months after irradiation, continued until one tumour shrank to less than 1 cm at 12 months, and the other disappeared completely at 24 months. In both cases functional integrity was restored, and neither radiation induced toxicity nor recurrence has occurred six years after treatment. The results in these two cases suggest that solid craniopharyngiomas are sensitive to interstitial irradiation. (author)

  6. Tumor interstitial fluid

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J.

    2013-01-01

    Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical...

  7. Interstitial granulomatous dermatitis (IGD)

    NARCIS (Netherlands)

    Tebeica, Tiberiu; Voicu, Cristiana; Patterson, James W.; Mangarov, Hristo; Lotti, T.; Wollina, Uwe; Lotti, Jacopo; França, Katlein; Batashki, Atanas; Tchernev, Georgi

    2017-01-01

    We report the case of a 42 years old male patient suffering from skin changes, which appeared in the last 7-8 years. Two biopsies were performed during the evolution of the lesion. Both showed similar findings that consisted in a busy dermis with interstitial, superficial and deep infiltrates of

  8. Idiopathic pulmonary fibrosis: evolving concepts.

    Science.gov (United States)

    Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H

    2014-08-01

    Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  9. Normal expiratory flow rate and lung volumes in patients with combined emphysema and interstitial lung disease: a case series and literature review.

    Science.gov (United States)

    Heathcote, Karen L; Cockcroft, Donald W; Fladeland, Derek A; Fenton, Mark E

    2011-01-01

    Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  10. Normal Expiratory Flow Rate and Lung Volumes in Patients with Combined Emphysema and Interstitial Lung Disease: A Case Series and Literature Review

    Directory of Open Access Journals (Sweden)

    Karen L Heathcote

    2011-01-01

    Full Text Available Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  11. Bronchoalveolar lavage: role in the pathogenesis, diagnosis, and management of interstitial lung disease

    International Nuclear Information System (INIS)

    Daniele, R.P.; Elias, J.A.; Epstein, P.E.; Rossman, M.D.

    1985-01-01

    Bronchoalveolar lavage has emerged as a useful technique for the study of pulmonary interstitial disorders. Several types of information are provided by the evaluation of lavage fluid. First, the identification of cellular constituents helps to separate inflammatory processes in which lymphocytes predominate (for example, sarcoidosis, hypersensitivity pneumonitis, and berylliosis) from those in which neutrophils or macrophages predominate (for example, idiopathic pulmonary fibrosis and histiocytosis X). Second, the cells removed during lavage can be studied for their immune properties and function; tested with specific antigens, in diseases such as berylliosis and hypersensitivity pneumonitis; and examined for the presence of unique surface antigens with monoclonal antibodies (for example, histiocytosis X). Third, in conjunction with scanning electron microscopy and electron probe analysis, lavage makes possible the identification of inorganic particles in alveolar macrophages of patients with pneumoconiotic lung disease. Finally, although lavage is still an investigative procedure for most pulmonary disorders, it has an established role in the diagnosis of opportunistic infections in the immunocompromised patient

  12. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  13. Pulmonary Fibrosis Foundation

    Science.gov (United States)

    ... submissions. MORE We Imagine a World Without Pulmonary Fibrosis The Pulmonary Fibrosis Foundation mobilizes people and resources to provide ... its battle against the deadly lung disease, pulmonary fibrosis (PF). PULMONARY FIBROSIS WALK SURPASSES PARTICIPATION AND FUNDRAISING GOALS Nearly ...

  14. Idiopathic Pulmonary Fibrosis: Diagnosis and Clinical Manifestations

    Science.gov (United States)

    Nakamura, Yutaro; Suda, Takafumi

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a parenchymal lung disease characterized by progressive interstitial fibrosis. The clinical course of IPF can be unpredictable and may be punctuated by acute exacerbations. Although much progress is being made in unraveling the mechanisms underlying IPF, effective therapy for improving survival remains elusive. Longitudinal disease profiling, especially in terms of clinical manifestations in a large cohort of patients, should lead to proper management of the patients and development of new treatments for IPF. Appropriate multidisciplinary assessment in ongoing registries is required to achieve this. This review summarizes the current status of the diagnosis and clinical manifestations of IPF. PMID:27625576

  15. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Khurram, Misbah; Skov, Lone; Rossen, Kristian

    2007-01-01

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

  16. Viral infection drives tissue fibrosis in vitro

    Directory of Open Access Journals (Sweden)

    Andrea P. Malizia

    2008-04-01

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

  17. Interstitial Granulomatous Dermatitis (IGD

    Directory of Open Access Journals (Sweden)

    Tiberiu Tebeica

    2017-07-01

    Full Text Available We report the case of a 42 years old male patient suffering from skin changes , which appeared in the last 7-8 years.  Two biopsies were performed during the evolution of the lesion. Both showed similar findings that consisted in a busy dermis with interstitial, superficial and deep infiltrates of lymphocytes and histiocytes dispersed among collagen bundles, with variable numbers of neutrophils scattered throughout. Some histiocytes were clustered in poorly formed granuloma that included rare giant cells, with discrete Palisades and piecemeal collagen degeneration, but without mucin deposition or frank necrobiosis of collagen. The clinical and histologic findings were supportive for interstitial granulomatous dermatitis. Interstitial granulomatous dermatitis (IGD is a poorly understood entity that was regarded by many as belonging to the same spectrum of disease or even synonym with palisaded and neutrophilic granulomatous dermatitis (PNGD. Although IGD and PNGD were usually related to connective tissue disease, mostly rheumatoid arthritis, some patients with typical histologic findings of IGD never develop autoimmune disorders, but they have different underlying conditions, such as metabolic diseases, lymphoproliferative disorders or other malignant tumours. These observations indicate that IGD and PNGD are different disorders with similar manifestations.

  18. Clinical Outcomes in Interstitial Lung Diseases : Measuring and improving quality of life

    NARCIS (Netherlands)

    M.J.G. Van Manen (Mirjam)

    2017-01-01

    markdownabstractInterstitial lung diseases (ILDs) contain a wide variety of disorders, usually affecting both lungs diffusely. The most common ILDs are idiopathic pulmonary fibrosis and sarcoidosis. ILDs have a major impact on quality of life. Although it is well-known that quality of life is

  19. Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment.

    Science.gov (United States)

    Khalil, Nasreen; O'Connor, Robert

    2004-07-20

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial pneumonia and are characterized by histological temporal heterogeneity, whereby normal lung tissue is interspersed with interstitial fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show restricted volumes and capacities, preserved flows and evidence of decreased gas exchange. High-resolution computed axial tomography demonstrates evidence of fibrosis and lung remodelling such as honeycomb cysts and traction bronchiectasis. There is no known effective treatment for IPF, but lung transplantation improves survival.

  20. Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Rubinstein, W.S.; Wenger, S.L.; Hoffman, R.M. [Univ. of Pittsburgh, PA (United States)] [and others

    1997-03-31

    We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderately severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,X-Y with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies. 49 refs., 2 figs., 1 tab.

  1. Interstitial pregnancy: role of MRI

    International Nuclear Information System (INIS)

    Filhastre, M.; Lesnik, A.; Dechaud, H.; Taourel, P.

    2005-01-01

    We report the MRI features of two cases of interstitial pregnancy. In both cases, MRI was able to localize the ectopic pregnancy by showing a gestational structure surrounded by a thick wall in the upper part of the uterine wall separated from the endometrium by an uninterrupted junctional zone. Because US may confuse angular and interstitial pregnancies and because interstitial pregnancy has a particular evolutive course, MR imaging may play a key role in the diagnosis and management of women with interstitial pregnancy. (orig.)

  2. rheumatoid arthritis associated with pulmonary fibrosis in nigerians

    African Journals Online (AJOL)

    Various pulmonary manifestations have been reported in the developed world, these include diffuse interstitial fibrosis ... system revealed pulse of 70bpm, BP 110/70 mmHg,. Apex beat not displaced, heart sounds I, II and normal. ... Other systems were essentially normal. Laboratory investigations showed elevated ESR.

  3. Jaccoud's arthropathy and pulmonary fibrosis in CREST syndrome

    International Nuclear Information System (INIS)

    Spinel B, Nestor; Montenegro, Pablo; Rondon Federico; Restrepo, Jose F; Iglesias G, Antonio

    2010-01-01

    We report a case of a 48 years old patient with diagnosis of incomplete CREST syndrome (variant limited systemic sclerosis) in who we documented the presence of Jaccoud's arthropathy of the hands and pulmonary involvement by pulmonary fibrosis type usual interstitial pneumonia, with positivity for rheumatoid factor and anti-cyclic citrullinated peptide antibody.

  4. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  5. Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

    NARCIS (Netherlands)

    Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

    2017-01-01

    Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

  6. Leptospira Interrogans Induces Fibrosis in the Mouse Kidney through Inos-Dependent, TLR- and NLR-Independent Signaling Pathways

    Science.gov (United States)

    Fanton d'Andon, Martine; Quellard, Nathalie; Fernandez, Béatrice; Ratet, Gwenn; Lacroix-Lamandé, Sonia; Vandewalle, Alain; Boneca, Ivo G.; Goujon, Jean-Michel; Werts, Catherine

    2014-01-01

    Background Leptospira (L.) interrogans are bacteria responsible for a worldwide reemerging zoonosis. Rodents carry L. interrogans asymptomatically in their kidneys and excrete bacteria in the urine, contaminating the environment. Humans get infected through skin contact and develop a mild or severe leptospirosis that may lead to renal failure and fibrosis. L. interrogans provoke an interstitial nephritis, but the induction of fibrosis caused by L. interrogans has not been studied in murine models. Innate immune receptors from the TLR and NLR families have recently been shown to play a role in the development and progression of tissue fibrosis in the lung, liver and kidneys under different pathophysiological situations. We recently showed that TLR2, TLR4, and NLRP3 receptors were crucial in the defense against leptospirosis. Moreover, infection of a human cell line with L. interrogans was shown to induce TLR2-dependent production of fibronectin, a component of the extracellular matrix. Therefore, we thought to assess the presence of renal fibrosis in L. interrogans infected mice and to analyze the contribution of some innate immune pathways in this process. Methodology/principal findings Here, we characterized by immunohistochemical studies and quantitative real-time PCR, a model of Leptospira-infected C57BL/6J mice, with chronic carriage of L. interrogans inducing mild renal fibrosis. Using various strains of transgenic mice, we determined that the renal infiltrates of T cells and, unexpectedly, TLR and NLR receptors, are not required to generate Leptospira-induced renal fibrosis. We also show that the iNOS enzyme, known to play a role in Leptospira-induced interstitial nephritis, also plays a role in the induction of renal fibrosis. Conclusion/significance To our knowledge, this work provides the first experimental murine model of sustained renal fibrosis induced by a chronic bacterial infection that may be peculiar, since it does not rely on TLR or NLR receptors

  7. Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Parra, Edwin Roger; Ruppert, Aline Domingos Pinto; Capelozzi, Vera Luiza

    2014-01-01

    To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.

  8. Usual interstitial pneumonitis UIP presenting with Wells grade 3. Can imaging methods help predict further progression of disease?; Fibrosi polmanare idiopatica con grado 3 di Wells all'esordio: possono le metodiche di diagnostica per immagini aiutare a predire la progressione ulteriore della malattia?

    Energy Technology Data Exchange (ETDEWEB)

    Fasano, L.; Pacilli, A. M.G. [Bologna Policlinico, Bologna (Italy). Ist. di Fisiopatologia Respiratoria; Zompatori, M.; Monetti, N. [Bologna Policlinico, Bologna (Italy). Servizio di Medicina Nucleare; Battista, G. [Bologna Policlinico, Bologna (Italy). Ist. di Radiologia, Radiodiagnostica 1; Di Scioscio, V.; Sciascia, N.

    1999-10-01

    Three different grades of idiopathic pulmonary fibrosis can be identified by HRCT pattern. Patients with predominant ground-glass opacity (grade 1) usually improve after treatment and may have a better prognosis. The subjects with a predominant reticular pattern and honeycombing (grade 3.) have irreversible fibrosis and usually do not improve after immunosuppressive therapy. Nevertheless, these patients may worsen even in the absence of HRCT features of the so-called alveolitis. The aim of this report is to investigate the predictive role of some noninvasive imaging methods (HRCT with visual score of disease extent; Gallium scintigraphy; DTPA scintigraphy) in patients with idiopathic fibrosis and a prevalent macroscopic fibrosis at HRCT study. [Italian] La fibrosi polomare idiopatica viene distinta in 3 gradi con diversa prognosi in base alla predominanza di opacita' a vetro smerigliato da alveolite o di fibrosi irreversibile. La fibrosi irreversibile tuttavia non e' necessariamente una situazione stabile ma puo progredire ed evolvere ulteriormente. In particolare i pazienti che gia all'esordio presentano solo i segni della fibrosi possono peggiorare a distanza di tempo nonostante la terapia. Scopo del lavoro e' stato quello di individuare in un gruppo di pazienti con prevalente fibrosi macroscopica quale possa essere un parametro preditivo della successiva evoluzione della malattia.

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

    Directory of Open Access Journals (Sweden)

    S. Mancin

    2011-09-01

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

  10. Interstitial shadow on chest CT is associated with the onset of interstitial lung disease caused by chemotherapeutic drugs

    International Nuclear Information System (INIS)

    Niho, Seiji; Goto, Koichi; Yoh, Kiyotaka; Kim, Y.H.; Ohmatsu, Hironobu; Kubota, Kaoru; Saijo, Nagahiro; Nishiwaki, Yutaka

    2006-01-01

    Pretreatment computerized tomography (CT) films of the chest was studied to clarify the influence of interstitial shadow on developing interstitial lung disease (ILD). Eligible patients were those lung cancer patients who started to receive first-line chemotherapy between October 2001 and March 2004. Patients who received thoracic radiotherapy to the primary lesion, mediastinum, spinal or rib metastases were excluded. We reviewed pretreatment conventional CT and plain X-ray films of the chest. Ground-glass opacity, consolidation or reticular shadow without segmental distribution was defined as interstitial shadow, with this event being graded as mild, moderate or severe. If interstitial shadow was detected on CT films of the chest, but not via plain chest X-ray, it was graded as mild. Patients developing ILD were identified from medial records. A total of 502 patients were eligible. Mild, moderate and severe interstitial shadow was identified in 7, 8 and 5% of patients, respectively. A total of 188 patients (37%) received tyrosine kinase inhibitor (TKI) treatment, namely gefitinib or erlotinib. Twenty-six patients (5.2%) developed ILD either during or after chemotherapy. Multivariate analyses revealed that interstitial shadow on CT films of the chest and treatment history with TKI were associated with the onset of ILD. It is recommended that patients with interstitial shadow on chest CT are excluded from future clinical trials until this issue is further clarified, as it is anticipated that use of chemotherapeutic agents frequently mediate onset of ILD in this context. (author)

  11. Pathogenic mechanism in lung fibrosis

    International Nuclear Information System (INIS)

    Witschi, H.; Haschek, W.M.; Meyer, K.R.; Ullrich, R.L.; Dalbey, W.E.

    1979-01-01

    The purpose of the study was to examine whether an interaction between two agents causing alveolar epithelial damage would produce lung fibrosis. In mouse lung, intraperitoneal injection of the antioxidant butylated hydroxytoluene causes diffuse alveolar type I cell necrosis, followed by proliferation of type II alveolar cells. In animals exposed to 70% O 2 or 100-200 rad x rays during the phase of type II cell proliferation following BHT, diffuse interstitial lung fibrosis developed within 2 weeks. Quantitative analysis of the lungs for hydroxyproline showed that the interaction between BHT and O 2 or x rays was synergistic. If exposure to O 2 or x rays was delayed until epithelial recovery was complete, no fibrosis was seen. Abnormally high levels of lung collagen persisted up to 6 months after one single treatment with BHT and 100 rad x rays. A commonly seen form of chronic lung damage may thus be caused by an acute interaction between a bloodborne agent which damages the alveolar cell and a toxic inhalant or x rays, provided a critically ordered sequence of exposure is observed

  12. Pulmonary fibrosis

    International Nuclear Information System (INIS)

    Yamakido, Michio; Okuzaki, Takeshi

    1992-01-01

    When the chest is exposed to x radiation and Co-60 gamma radiation, radiation damage may occur in the lungs 2 to 10 weeks after irradiation. This condition is generally referred to as radiation pneumonitis, with the incidence ranging from 5.4% to 91.8% in the literature. Then radiation pneumonitis may develop into pulmonary fibrosis associated with roentgenologically diffuse linear and ring-like shadows and strong contraction 6 months to one year after irradiation. Until recently, little attention has been paid to pulmonary pneumonitis as a delayed effect of A-bomb radiation. The recent study using the population of 9,253 A-bomb survivors have suggested that the prevalence of pulmonary fibrosis tended to be high in heavily exposed A-bomb survivors. Two other studies using the cohort of 16,956 and 42,728 A-bomb survivors, respectively, have shown that the prevalence of roentgenologically proven pulmonary fibrosis was higher in men than women (1.82% vs 0.41%), was increased with aging and had a higher tendency in heavily exposed A-bomb survivors. (N.K.)

  13. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter

    2008-01-01

    PURPOSE OF REVIEW: The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. RECENT FINDINGS: Epidemiological and histochemical studies demonstrated....... Increasingly poor renal function, aberrations in calcium-phosphate metabolism and erythropoietin treatment seem to increase the risk of the disease and its severity. Up to 25-30% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. The figure...... that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. One particular agent, gadodiamide, caused the majority of cases, but gadopentetate dimeglumine has also been implicated in several cases...

  14. Tumorous interstitial lung disease

    International Nuclear Information System (INIS)

    Dinkel, E.; Meyer, E.; Mundinger, A.; Helwig, A.; Blum, U.; Wuertemberger, G.

    1990-01-01

    The radiological findings in pulmonary lymphangitic carcinomatosis and in leukemic pulmonary infiltrates mirror the tumor-dependent monomorphic interstitial pathology of lung parenchyma. It is a proven fact that pulmonary lymphangitic carcinomatosis is caused by hematogenous tumor embolization to the lungs; pathogenesis by contiguous lymphangitic spread is the exception. High-resolution CT performed as a supplement to the radiological work-up improves the sensitivity for pulmonary infiltrates in general and thus makes the differential diagnosis decided easier. Radiological criteria cannot discriminate the different forms of leukemia. Plain chest X-ray allows the diagnosis of pulmonary involvement in leukemia due to tumorous infiltrates and of tumor- or therapy-induced complications. It is essential that the radiological findings be interpreted with reference to the stage of tumor disease and the clinical parameters to make the radiological differential diagnosis of opportunistic infections more reliable. (orig.) [de

  15. Interstitial irradiation of rectal carcinoma with rectal template

    International Nuclear Information System (INIS)

    Ikeda, Hiroshi; Nishiyama, Kinji; Tanaka, Ken; Nakanishi, Makoto; Inoue, Takehiro

    1984-01-01

    Using Iridium-192 wires through a rectal template after Syed, interstitial brachytherapy was conducted in a patient with inoperable adenocarcinoma of the rectum. 67-year-old man with constipation and change in the stool caliber underwent external radiotherapy (4,000cGy/4W) to the whole pelvis including the perineum, followed by interstitial implant using a template, at the Department of Radiology, Osaka University Hospital. Marked tumor regression, marked circumferential fibrosis and a remarkable decline of CEA titers (pre-RT: 35.8ng/ml, post-RT: 6.2ng/ml) were observed until 7 months post-RT. The domestic production of Iridium-192 wires has made possible the intergrated use of brachytherapy in the perineal region in Japan. (author)

  16. A pilot study: a combined therapy using polymyxin-B hemoperfusion and extracorporeal membrane oxygenation for acute exacerbation of interstitial pneumonia.

    Science.gov (United States)

    Itai, Junji; Ohshimo, Shinichiro; Kida, Yoshiko; Ota, Kohei; Iwasaki, Yasumasa; Hirohashi, Nobuyuki; Bonella, Francesco; Guzman, Josune; Costabel, Ulrich; Kohno, Nobuoki; Tanigawa, Koichi

    2015-01-05

    Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) might be beneficial for treating acute exacerbation (AE) of interstitial pneumonia (IP). Venovenous extracorporeal membranous oxygenation (VV-ECMO) is an emerging tool to avoid ventilator-induced lung injury. This is a report presenting the first three patients with AE of IP treated with a combined therapy of PMX-DHP and VV-ECMO. Patient 1 was a 68-year-old male with acute interstitial pneumonia, patient 2 a 67-year-old male with AE of idiopathic pulmonary fibrosis, and patient 3 a 61-year-old female with AE of collagen vascular disease-associated interstitial pneumonia. All patients were severely hypoxemic and required mechanical ventilation. A combined therapy using PMX-DHP and VV-ECMO was initiated with support of intravenous corticosteroids and antibiotics. Radiological findings, oxygenation and laboratory findings markedly improved and all patients survived without severe complications. A combined therapy of PMX-DHP and VV-ECMO might be a therapeutic option for AE of IP.

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

    Science.gov (United States)

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

    2017-10-01

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

  18. Venous Thromboembolism and Risk of Idiopathic Interstitial Pneumonia A Nationwide Study

    DEFF Research Database (Denmark)

    Sode, Birgitte Margareta; Dahl, Morten; Nielsen, Sune Fallgaard

    2010-01-01

    Rationale: Idiopathic interstitial pneumonia is characterized by pulmonary fibrosis and high mortality. Objectives: We examined the association between ever-diagnosed venous thromboembolism and risk of incident idiopathic interstitial pneumonia. Venous thromboembolism was taken as a proxy...... Danish registries. Measurements and Main Results: Age-standardized incidence rates per 10,000 person-years for idiopathic interstitial pneumonia were higher among those ever diagnosed with venous thromboembolism (1.8; n = 158,676), pulmonary embolism (2.8; n = 70,586), and deep venous thrombosis only (1.......2; n = 88,090), than among control subjects (0.8; n = 7,260,278). Multivariate-adjusted hazard ratios for idiopathic interstitial pneumonia were 1.8 (95% confidence interval [Cl], 1.7-1.9) in those ever diagnosed with venous thromboembolism, 2.4 (95% CI, 2.3-2.6) in those ever diagnosed with pulmonary...

  19. Evaluation of matrix metalloproteinases-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 (TIMP-2) in oral submucous fibrosis and their correlation with disease severity.

    Science.gov (United States)

    Shrestha, A; Carnelio, S

    2013-01-01

    Oral submucous fibrosis (OSF), a potentially malignant oral lesion, is a form of pathological fibrosis affecting the oral mucosa. It results from an imbalance in equilibrium of the normal process of synthesis and degradation of extra cellular matrix. Matrix metalloproteinases and its inhibitors play important role in remodeling of the extra cellular matrix which are important in progression and pathogenesis of potentially malignant lesions to malignancy. To evaluate the expression and distribution of Matrix metalloproteinases-2 (MMP- 2) and Tissue inhibitor of metalloproteinases-2 (TIMP-2) in different grades of Oral Submucous Fibrosis(OSF). Immunohistochemical analysis for MMP-2 and its TIMP-2 was performed in 30 histopathologically confirmed, formalin fixed, paraffin embedded specimens of OSF. A semi-quantitative analysis was done to assess the expression, distribution and comparison of these in various stages of this disease. All moderately advanced cases and 64.2% for MMP-2 and 78.5% for TIMP-2 of early stage cases showed positivity. Between two stages of OSF, statistically significant differences were noted in expression of TIMP-2 in lamina propria, deep connective tissue and supra basal layers (p<0.05) and basal and supra basal layers for MMP-2 (p<0.05). The simultaneous increase in expression of MMP-2 and TIMP-2 with advancing stages of OSF can provide a basis for considering the proteases as important mediators in the pathogenesis and progression of OSF which could aid in identifying the aggressiveness of the condition and elucidate its role in its malignant transformation.

  20. Idiopathic pulmonary fibrosis with complication of severe respiratory failure, right heart failure, and steroid induced diabetes – qualification for lung transplantation as a matter of urgency

    Directory of Open Access Journals (Sweden)

    Beata P. Kraśnicka-Sokół

    2016-09-01

    Full Text Available A 62-year-old woman 146 cm tall and weighing 50 kg, due to idiopathic pulmonary fibrosis, was firstly approved for lung transplantation according to the planned mode. Due to the low height of the patient there were difficulties in the selection of the donor and prolonged waiting time for the surgery. Rapid progression of pulmonary hypertension and steroid-induced diabetes forced us to change the mode of the procedure to urgent. The description of the case shows the difficulties in therapy and choosing the appropriate time for lung transplantation. In this case, the collaboration of specialists from various fields in the decision on transplant is noteworthy.

  1. Rheumatoid arthritis associated interstitial lung disease: a review

    Directory of Open Access Journals (Sweden)

    Deborah Assayag

    2014-04-01

    Full Text Available Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the population. Interstitial lung disease is a serious and frequent complication of rheumatoid arthritis. Rheumatoid arthritis associated interstitial lung disease (RA-ILD is characterized by several histopathologic subtypes. This article reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline the important steps involved in the work-up of RA-ILD and review the evidence for treatment and prognosis.

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

    Directory of Open Access Journals (Sweden)

    Bonella F

    2015-12-01

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

  3. CT and conventional radiographic techniques in interstitial pulmonary disease

    International Nuclear Information System (INIS)

    Leipner, N.; Schueller, H.; Uexkuell-Gueldenband, V. v.; Schlolaut, K.H.; Overlack, A.; Bonn Univ.

    1988-01-01

    One hundred and sixty-four patients with pulmonary fibrosis were examined by CT and by conventional radiological methods. Sixty patients had asbestosis, thirty-nine silicosis, forty sarcoidosis and twenty-five had idiopathic pulmonary fibrosis. CT is superior to conventional radiography in evaluating interstitial pulmonary changes, particularly of the pleura and the lung parenchyma. In sixty-nine patients there were some findings which could only be demonstrated by CT. In asbestosis, silicosis and sarcoidosis the CT classification of the lung parenchyma which we have suggested produces significantly better correlation with vital capacity than can be achieved from conventional chest films, according to the guidelines of the I.L.O. (orig./GDG) [de

  4. Consensus document for the diagnosis and treatment of idiopathic pulmonary fibrosis: Joint Consensus of Sociedade Portuguesa de Pneumologia, Sociedade Portuguesa de Radiologia e Medicina Nuclear e Sociedade Portuguesa de Anatomia Patológica.

    Science.gov (United States)

    Robalo Cordeiro, C; Campos, P; Carvalho, L; Campainha, S; Clemente, S; Figueiredo, L; Jesus, J M; Marques, A; Souto-Moura, C; Pinto Basto, R; Ribeiro, A; Serrado, M; Morais, A

    2016-01-01

    Idiopathic pulmonary fibrosis is a rare interstitial lung disease included in the Idiopathic Interstitial Pneumonias group. Although several potential risk factors have been described, it is a progressive fibrosing disease of unknown cause affecting mainly adults over 50 years and associated with a poor prognosis, reflected in a median survival of 2-3 years after diagnosis. The concept of a multidisciplinary working group for the diagnosis of idiopathic pulmonary fibrosis is based on the need to have experienced pulmonologists, radiologists and pathologists in the evaluation and correct treatment of the disease, and requires the use of all available data about individual patients, standardized (largely through High Resolution Computed Tomography and pathology when needed) as well as non-standardized data (laboratory, serology and biomarkers). This approach helps to increase diagnostic accuracy and is an internationally accepted recommendation. In regard to therapy, the situation has changed radically since the publication of the ATS/ERS/JRS/ALAT 2011 guidelines on the diagnosis and management of idiopathic pulmonary fibrosis where it was stressed that no proven therapy exists for this disease. Currently besides non-pharmacological treatment, therapy of complications and comorbidities and palliative care, nintedanib and pirfenidone, two compounds with pleiotropic mechanisms of action, are to date, the two drugs with confirmed efficacy in slowing functional decline and disease progression in idiopathic pulmonary fibrosis patients. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

  5. L-Endoglin Overexpression Increases Renal Fibrosis after Unilateral Ureteral Obstruction

    Science.gov (United States)

    Arévalo, Miguel; Núñez-Gómez, Elena; Pérez-Roque, Lucía; Pericacho, Miguel; González-Núñez, María; Langa, Carmen; Martínez-Salgado, Carlos; Perez-Barriocanal, Fernando; Bernabeu, Carmelo; Lopez-Novoa, José M.

    2014-01-01

    Transforming growth factor-β (TGF-β) plays a pivotal role in renal fibrosis. Endoglin, a 180 KDa membrane glycoprotein, is a TGF-β co-receptor overexpressed in several models of chronic kidney disease, but its function in renal fibrosis remains uncertain. Two membrane isoforms generated by alternative splicing have been described, L-Endoglin (long) and S-Endoglin (short) that differ from each other in their cytoplasmic tails, being L-Endoglin the most abundant isoform. The aim of this study was to assess the effect of L-Endoglin overexpression in renal tubulo-interstitial fibrosis. For this purpose, a transgenic mouse which ubiquitously overexpresses human L-Endoglin (L-ENG+) was generated and unilateral ureteral obstruction (UUO) was performed in L-ENG+ mice and their wild type (WT) littermates. Obstructed kidneys from L-ENG+ mice showed higher amounts of type I collagen and fibronectin but similar levels of α-smooth muscle actin (α-SMA) than obstructed kidneys from WT mice. Smad1 and Smad3 phosphorylation were significantly higher in obstructed kidneys from L-ENG+ than in WT mice. Our results suggest that the higher increase of renal fibrosis observed in L-ENG+ mice is not due to a major abundance of myofibroblasts, as similar levels of α-SMA were observed in both L-ENG+ and WT mice, but to the higher collagen and fibronectin synthesis by these fibroblasts. Furthermore, in vivo L-Endoglin overexpression potentiates Smad1 and Smad3 pathways and this effect is associated with higher renal fibrosis development. PMID:25313562

  6. Interstitial lung involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    David Vladimirovich Bestaev

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune rheumatic disease of unknown etiology, characterized by chronic erosive arthritis and extraarticular manifestations. Pulmonary involvement is one of the common extraarticular manifestations of RA and may show itself as bronchial tree lesions, rheumatoid nodules, Caplan's syndrome, and lesions in the pleura or pulmonary interstitium (interstitial lung involvement (ILI. High-resolution computed tomography allows the diagnosis of ILI in RA in nearly 70% of cases although the incidence of ILI may be lower (4 to 30% depending on diagnostic methods and patient selection criteria. There are several histopathological types of ILI, the differential diagnosis of which can be troublesome. Usual interstitial pneumonia (UIP and nonspecific interstitial pneumonia are major types of RA-associated ILI. UIP-pattern ILI has a more severe course than ILI with other histological patterns. The clinical presentation of ILI may be complicated by the likely toxic effect of a number of disease-modifying antirheumatic drugs (DMARDs used to treat RA, such as methotrexate and leflunomide, and biological agents (BAs, tumor necrosis factor-α (TNF-α inhibitors. The pathogenesis of pulmonary involvement in RA and the role of synthetic DMARDs and BAs in the development of ILI call for further investigations.An extraarticular manifestation, such as ILI, affects the choice of treatment policy in patients with RA.The relevance of a study of ILI is beyond question. The paper discusses the state-of-the-art of investigations in this area.

  7. Increased circulating miR-21 levels are associated with kidney fibrosis.

    Directory of Open Access Journals (Sweden)

    François Glowacki

    Full Text Available MicroRNAs (miRNAs are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA. Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001. By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03, and between miR-21 levels and aMDRD (ß = -0.398, p = 0.006. Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.

  8. Role of Receptor Tyrosine Kinase Signaling in Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Feng Liu

    2016-06-01

    Full Text Available Renal fibrosis can be induced in different renal diseases, but ultimately progresses to end stage renal disease. Although the pathophysiologic process of renal fibrosis have not been fully elucidated, it is characterized by glomerulosclerosis and/or tubular interstitial fibrosis, and is believed to be caused by the proliferation of renal inherent cells, including glomerular epithelial cells, mesangial cells, and endothelial cells, along with defective kidney repair, renal interstitial fibroblasts activation, and extracellular matrix deposition. Receptor tyrosine kinases (RTKs regulate a variety of cell physiological processes, including metabolism, growth, differentiation, and survival. Many studies from in vitro and animal models have provided evidence that RTKs play important roles in the pathogenic process of renal fibrosis. It is also showed that tyrosine kinases inhibitors (TKIs have anti-fibrotic effects in basic research and clinical trials. In this review, we summarize the evidence for involvement of specific RTKs in renal fibrosis process and the employment of TKIs as a therapeutic approach for renal fibrosis.

  9. Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

    Science.gov (United States)

    Lee, Chun Geun; Herzog, Erica L.; Ahangari, Farida; Zhou, Yang; Gulati, Mridu; Lee, Chang-Min; Peng, Xueyan; Feghali-Bostwick, Carol; Jimenez, Sergio A.; Varga, John; Elias, Jack A.

    2014-01-01

    Interstitial lung disease (ILD) with pulmonary fibrosis is an important manifestation in systemic sclerosis (SSc, scleroderma) where it portends a poor prognosis. However, biomarkers that predict the development and or severity of SSc-ILD have not been validated, and the pathogenetic mechanisms that engender this pulmonary response are poorly understood. In this study, we demonstrate in two different patient cohorts that the levels of chitotriosidase (Chit1) bioactivity and protein are significantly increased in the circulation and lungs of SSc patients compared with demographically matched controls. We also demonstrate that, compared with patients without lung involvement, patients with ILD show high levels of circulating Chit1 activity that correlate with disease severity. Murine modeling shows that in comparison with wild-type mice, bleomycin-induced pulmonary fibrosis was significantly reduced in Chit1−/− mice and significantly enhanced in lungs from Chit1 overexpressing transgenic animals. In vitro studies also demonstrated that Chit1 interacts with TGF-β1 to augment fibroblast TGF-β receptors 1 and 2 expression and TGF-β–induced Smad and MAPK/ERK activation. These studies indicate that Chit1 is potential biomarker for ILD in SSc and a therapeutic target in SSc-associated lung fibrosis and demonstrate that Chit1 augments TGF-β1 effects by increasing receptor expression and canonical and noncanonical TGF-β1 signaling. PMID:22826322

  10. Gallium interstitial contributions to diffusion in gallium arsenide

    Science.gov (United States)

    Schick, Joseph T.; Morgan, Caroline G.

    2011-09-01

    A new diffusion path is identified for gallium interstitials, which involves lower barriers than the barriers for previously identified diffusion paths [K. Levasseur-Smith and N. Mousseau, J. Appl. Phys. 103, 113502 (2008), P. A. Schultz and O. A. von Lilienfeld, Modelling and Simulation in Materials Science and Engineering 17, 084007 (2009)] for the charge states which dominate diffusion over most of the available range of Fermi energies. This path passes through the ⟨110⟩ gallium-gallium split interstitial configuration, and has a particularly low diffusion barrier of 0.35 eV for diffusion in the neutral charge state. As a part of this work, the character of the charge states for the gallium interstitials which are most important for diffusion is investigated, and it is shown that the last electron bound to the neutral interstitial occupies a shallow hydrogenic bound state composed of conduction band states for the hexagonal interstitial and both tetrahedral interstitials. How to properly account for the contributions of such interstitials is discussed for density-functional calculations with a k-point mesh not including the conduction band edge point. Diffusion barriers for gallium interstitials are calculated in all the charge states which can be important for a Fermi level anywhere in the gap, q = 0, +1, +2, and +3, for diffusion via the ⟨110⟩ gallium-gallium split interstitial configuration and via the hexagonal interstitial configuration. The lowest activation enthalpies over most of the available range of Fermi energies are found to correspond to diffusion in the neutral or singly positive state via the ⟨110⟩ gallium-gallium split interstitial configuration. It is shown that several different charge states and diffusion paths contribute significantly for Fermi levels within 0.2 eV above the valence band edge, which may help to explain some of the difficulties [H. Bracht and S. Brotzmann, Phys. Rev. B 71, 115216 (2005)] which have been

  11. Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Takahashi, Youhei; Saito, Atsushi; Chiba, Hirofumi; Kuronuma, Koji; Ikeda, Kimiyuki; Kobayashi, Tomofumi; Ariki, Shigeru; Takahashi, Motoko; Sasaki, Yasushi; Takahashi, Hiroki

    2018-02-27

    Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. Although IPF has not been thought to be associated with bacterial communities, recent papers reported the possible role of microbiome composition in IPF. The roles of microbiomes in respiratory functions and as clinical biomarkers for IPF remain unknown. In this study, we aim to identify the relationship between the microbial environment in the lung and clinical findings. Thirty-four subjects diagnosed with IPF were included in this analysis. The 16S rDNA was purified from bronchoalveolar lavage fluid obtained at the time of diagnosis and analyzed using next-generation sequencing techniques to characterize the bacterial communities. Furthermore, microbiomes from mice with bleomycin-induced lung fibrosis were analyzed. The most prevalent lung phyla were Firmicutes, Proteobacteria and Bacteroidetes. Decreased microbial diversity was found in patients with low forced vital capacity (FVC) and early mortality. Additionally, the diversity and relative abundance of Firmicutes, Streptococcaceae, and Veillonellaceae were significantly associated with FVC, 6-min walk distance, and serum surfactant protein D. Bleomycin-induced lung fibrosis resulted in decrease of diversity and alteration of microbiota in PCoA analysis. These results support the observations in human specimens. This study identified relationships between specific taxa in BALF and clinical findings, which were also supported by experiments in a mouse model. Our data suggest the possibility that loss of microbial diversity is associated with disease activities of IPF.

  12. Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis.

    Science.gov (United States)

    Zhou, Dong; Fu, Haiyan; Zhang, Lu; Zhang, Ke; Min, Yali; Xiao, Liangxiang; Lin, Lin; Bastacky, Sheldon I; Liu, Youhua

    2017-08-01

    Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β -catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro , incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication. Copyright © 2017 by the American Society of Nephrology.

  13. Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Lili eGao

    2015-10-01

    Full Text Available Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA, a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition and activation of tansforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

  14. Chronic interstitial lung disease in children

    Directory of Open Access Journals (Sweden)

    Matthias Griese

    2018-02-01

    Full Text Available Children's interstitial lung diseases (chILD are increasingly recognised and contain many lung developmental and genetic disorders not yet identified in adult pneumology. Worldwide, several registers have been established. The Australasian Registry Network for Orphan Lung Disease (ARNOLD has identified problems in estimating rare disease prevalence; focusing on chILD in immunocompetent patients, a period prevalence of 1.5 cases per million children and a mortality rate of 7% were determined. The chILD-EU register highlighted the workload to be covered per patient included and provided protocols for diagnosis and initial treatment, similar to the United States chILD network. Whereas case reports may be useful for young physicians to practise writing articles, cohorts of patients can catapult progress, as demonstrated by recent studies on persistent tachypnoea of infancy, hypersensitivity pneumonitis in children and interstitial lung disease related to interferonopathies from mutations in transmembrane protein 173. Translational research has linked heterozygous mutations in the ABCA3 transporter to an increased risk of interstitial lung diseases, not only in neonates, but also in older children and adults. For surfactant dysfunction disorders in infancy and early childhood, lung transplantation was reported to be as successful as in adult patients. Mutual potentiation of paediatric and adult pneumologists is mandatory in this rapidly extending field for successful future development. This brief review highlights publications in the field of paediatric interstitial lung disease as reviewed during the Clinical Year in Review session presented at the 2017 European Respiratory Society (ERS Annual Congress in Milan, Italy. It was commissioned by the ERS and critically presents progress made as well as drawbacks.

  15. MRI of interstitial lung diseases. What is possible?

    International Nuclear Information System (INIS)

    Biederer, J.; Wielpuetz, M.O.; Jobst, B.J.; Dinkel, J.

    2014-01-01

    Magnetic resonance imaging (MRI) of the lungs is becoming increasingly appreciated as a third diagnostic imaging modality besides chest x-ray and computed tomography (CT). Its value is well acknowledged for pediatric patients or for scientific use particularly when radiation exposure should be strictly avoided. However, the diagnosis of interstitial lung disease is the biggest challenge of all indications. The objective of this article is a summary of the current state of the art for diagnostic MRI of interstitial lung diseases. This article reflects the results of a current search of the literature and discusses them against the background of the authors own experience with lung MRI. Due to its lower spatial resolution and a higher susceptibility to artefacts MRI does not achieve the sensitivity of CT for the detection of small details for pattern recognition (e.g. fine reticulation and micronodules) but larger details (e.g. coarse fibrosis and honeycombing) can be clearly visualized. Moreover, it could be shown that MRI has the capability to add clinically valuable information on regional lung function (e.g. ventilation, perfusion and mechanical properties) and inflammation with native signal and contrast dynamics. In its present state MRI can be used for comprehensive cardiopulmonary imaging in patients with sarcoidosis or for follow-up of lung fibrosis after initial correlation with CT. Far more indications are expected when the capabilities of MRI for the assessment of regional lung function and activity of inflammation can be transferred into robust protocols for clinical use. (orig.) [de

  16. "Tipping" extracellular matrix remodeling towards regression of liver fibrosis

    DEFF Research Database (Denmark)

    Magdaleno, Fernando; Schierwagen, Robert; Uschner, Frank E

    2018-01-01

    Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established...... fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, together with other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration...

  17. Changes of serum levels of prealbumin (PAB), cholinesterase (CHE), total bile acid (TBA) and ALT as related to the severity of inflammatory process and hepatic fibrosis in patients with chronic virus B hepatitis

    International Nuclear Information System (INIS)

    Chi Xiaoxia; Chen Jianxiong; Xiong Ying

    2005-01-01

    Objective: To study the correlationship between the serum levels of PAB, CHE, TBA, ALT and the severity of the disease process in patients with chronic virus B hepatitis. Methods: Serum levels of PAB, CHE, ALT (with biochemical methods) and TBA (with RIA) were examined in 93 patients with biopsy proven virus B hepatitis and 46 controls. Results: The 93 patients were of two groups: a less advanced group (n=51) and a more advanced group (n=42). Serum TBA, ALT levels were significnatly higher and serum PAB, CHE levels were significantly lower in the more advanced group than those in the less advanced group (P 0 to s 4 . Changes of levels of ALT were of no regular pattern, but serum levels of TBA regularly increased and levels of PAB, CHE regularly decreased as the fibrosis grading proceeded from s 0 to s 4 and the differences between the levels in s 4 and any other grading were significant (P<0.01). Conclusion: Combined determination of these serum markers might reflect the degree of inflammatory process and hepatic fibrosis in patients with virus B hepatitis, leading to earlier detection of cirrhosis. (authors)

  18. Guidelines for the medical treatment of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Xaubet, Antoni; Molina-Molina, María; Acosta, Orlando; Bollo, Elena; Castillo, Diego; Fernández-Fabrellas, Estrella; Rodríguez-Portal, José Antonio; Valenzuela, Claudia; Ancochea, Julio

    2017-05-01

    Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    Science.gov (United States)

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  20. Hyper-activated pro-inflammatory CD16 monocytes correlate with the severity of liver injury and fibrosis in patients with chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Ji-Yuan Zhang

    Full Text Available BACKGROUND: Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT carriers and 78 immune activated (IA patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16(+ subsets, which were closely associated with serum alanine aminotransferase (ALT levels and the liver histological activity index (HAI scores. In addition, the increased CD16(+ monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16(- monocytes/macrophages. Furthermore, peripheral blood CD16(+ monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores. CONCLUSIONS: These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease.

  1. Interstitial cystitis: painful bladder syndrome

    Directory of Open Access Journals (Sweden)

    R F Sholan

    2018-02-01

    Full Text Available Interstitial cystitis, or painful bladder syndrome, is a chronic inflammatory disease of a bladder of unknown etiology. It negatively affects the quality of life, causes depressive disorders, anxiety, and sexual dysfunction. Despite numerous studies, the etiology of interstitial cystitis is still unclear and it’s considered as painful bladder syndrome with multifactorial origin. According to the US National Health and Nutrition Examination Survey, 470/100 000 people (60/100 000 men, 850/100 000 women are diagnosed with interstitial cystitis. Diagnosis of the disease is difficult and is substantially based on clinical symptoms. Pelvic pain, urinary urgency, frequency and nocturia are the basic complaints in this pathology. The diagnosis requires exclusion of diseases with similar manifestations. So interstitial cystitis is frequently misdiagnosed as urinary tract infection, overactive bladder, urethral obstruction or diverticulosis, chronic prostatitis, bladder cancer, vulvodynia, endometriosis, and chronic pelvic pain. Etiopathogenesis of the disease is uncertain, which makes etiologic treatment impossible. Currently scientific discussions on the causes of disease continue as well as different treatment regimens are offered, but are often ineffective, palliative and temporary. The treatment for intersticial cystitis should focus on restoring normal bladder function, prevention of relapse of symptoms and improvement of patients’ quality of life. The literature review presents current view on the terminology, epidemiology, diagnosis and treatment of interstitial cystitis.

  2. Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

    LENUS (Irish Health Repository)

    O'Dwyer, David N

    2013-10-01

    Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD.

  3. Interstitial Fluid Flow: The Mechanical Environment of Cells and Foundation of Meridians

    Directory of Open Access Journals (Sweden)

    Wei Yao

    2012-01-01

    Full Text Available Using information from the deep dissection, microobservation, and measurement of acupoints in the upper and lower limbs of the human body, we developed a three-dimensional porous medium model to simulate the flow field using FLUENT software and to study the shear stress on the surface of interstitial cells (mast cells caused by interstitial fluid flow. The numerical simulation results show the following: (i the parallel nature of capillaries will lead to directional interstitial fluid flow, which may explain the long interstitial tissue channels or meridians observed in some experiments; (ii when the distribution of capillaries is staggered, increases in the velocity alternate, and the velocity tends to be uniform, which is beneficial for substance exchange; (iii interstitial fluid flow induces a shear stress, with magnitude of several Pa, on interstitial cell membranes, which will activate cells and lead to a biological response; (iv capillary and interstitial parameters, such as capillary density, blood pressure, capillary permeability, interstitial pressure, and interstitial porosity, affect the shear stress on cell surfaces. The numerical simulation results suggest that in vivo interstitial fluid flow constitutes the mechanical environment of cells and plays a key role in guiding cell activities, which may explain the meridian phenomena and the acupuncture effects observed in experiments.

  4. Comorbid Conditions in Idiopathic Pulmonary Fibrosis: Recognition and Management

    Directory of Open Access Journals (Sweden)

    Justin M. Oldham

    2017-08-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF, a fibrosing interstitial pneumonia of unknown etiology, primarily affects older adults and leads to a progressive decline in lung function and quality of life. With a median survival of 3–5 years, IPF is the most common and deadly of the idiopathic interstitial pneumonias. Despite the poor survivorship, there exists substantial variation in disease progression, making accurate prognostication difficult. Lung transplantation remains the sole curative intervention in IPF, but two anti-fibrotic therapies were recently shown to slow pulmonary function decline and are now approved for the treatment of IPF in many countries around the world. While the approval of these therapies represents an important first step in combatting of this devastating disease, a comprehensive approach to diagnosing and treating patients with IPF remains critically important. Included in this comprehensive assessment is the recognition and appropriate management of comorbid conditions. Though IPF is characterized by single organ involvement, many comorbid conditions occur within other organ systems. Common cardiovascular processes include coronary artery disease and pulmonary hypertension (PH, while gastroesophageal reflux and hiatal hernia are the most commonly encountered gastrointestinal disorders. Hematologic abnormalities appear to place patients with IPF at increased risk of venous thromboembolism, while diabetes mellitus (DM and hypothyroidism are prevalent metabolic disorders. Several pulmonary comorbidities have also been linked to IPF, and include emphysema, lung cancer, and obstructive sleep apnea. While the treatment of some comorbid conditions, such as CAD, DM, and hypothyroidism is recommended irrespective of IPF, the benefit of treating others, such as gastroesophageal reflux and PH, remains unclear. In this review, we highlight common comorbid conditions encountered in IPF, discuss disease-specific diagnostic

  5. Interstitial inflammatory lesions of the pulmonary allograft: a retrospective analysis of 2697 transbronchial biopsies

    DEFF Research Database (Denmark)

    Burton, C.M.; Iversen, M.; Carlsen, J.

    2008-01-01

    . The strongest histological correlations were between ACR and lymphocytic bronchiolitis (OR 5.1, Pfibrosis (OR 3.2, Ppulmonary hemosiderosis were also more likely to demonstrate the finding of interstitial fibrosis (OR 3.0 and 3.7, P..., incidence and possible associations between commonly identified inflammatory and fibrotic lesions in the pulmonary allograft. METHODS: Retrospective chart review of all transbronchial biopsies performed within the first 2 years of 299 lung-transplanted patients in the period 1996 to 2006. RESULTS: A total...... (BOOP) and interstitial pneumonitis occurred at 4 to 6 weeks, and 6 to 12 weeks, respectively. There was a steady increase in the cumulative proportion of patients with fibrosis and bronchiolitis obliterans, at each successive scheduled surveillance time point beyond 3 months posttransplantation...

  6. Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development

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    Yoshiro Kai

    2017-03-01

    Full Text Available Pulmonary fibrosis is a progressive lung disorder characterized by interstitial fibrosis, for which no effective treatments are available. Chondroitin sulfate proteoglycan (CSPG has been shown to be a mediator, but the specific component of glycosaminoglycan chains of CSPG has not been explored. We show that chondroitin sulfate E-type (CS-E is involved in fibrogenesis. Small interfering RNA (siRNA targeting carbohydrate sulfotransferase 15 (CHST15 was designed to inhibit CHST15 mRNA and its product, CS-E. CS-E augments cell contraction and CHST15 siRNA inhibits collagen production. We found that bleomycin treatment increased CHST15 expression in interstitial fibroblasts at day 14. CHST15 siRNA was injected intranasally on days 1, 4, 8, and 11, and CHST15 mRNA was significantly suppressed by day 14. CHST15 siRNA reduced lung CSPG and the grade of fibrosis. CHST15 siRNA repressed the activation of fibroblasts, as evidenced by suppressed expression of α smooth muscle actin (αSMA, connective tissue growth factor (CTGF, lysyl oxidase like 2 (LOXL2, and CC-chemokine ligand 2 (CCL2/monocyte chemoattractant protein-1 (MCP-1. Inflammatory infiltrates in the bronchoalveolar lavage fluid (BALF and interstitium were diminished by CHST15 siRNA. These results indicate a pivotal role for CHST15 in fibroblast-mediated lung fibrosis and suggest a possible new therapeutic role for CHST15 siRNA in pulmonary fibrosis.

  7. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis

    2001-11-01

    Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

  8. Update on diagnosis and treatment of idiopathic pulmonary fibrosis

    Science.gov (United States)

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

    2015-01-01

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

  9. Update on diagnosis and treatment of idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    José Baddini-Martinez

    2015-10-01

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

  10. Exhaled ethane: an in vivo biomarker of lipid peroxidation in interstitial lung diseases.

    Science.gov (United States)

    Kanoh, Soichiro; Kobayashi, Hideo; Motoyoshi, Kazuo

    2005-10-01

    Oxidative stress plays a role in the pathogenesis and progression of interstitial lung disease (ILD). Exhaled ethane is a product of lipid peroxidation that has been proposed as a biomarker of oxidative stress in vivo. To determine whether the exhaled ethane level is elevated in patients with ILD and to compare it with other clinical parameters. Breath samples were collected from 34 patients with ILD, including 13 with idiopathic pulmonary fibrosis (IPF), 9 patients with cryptogenic organizing pneumonia, 6 patients with collagen vascular disease-associated interstitial pneumonia, and 6 patients with pulmonary sarcoidosis. Gas samples were obtained at hospital admission and after 3 weeks. After each expired sample was concentrated using a trap-and-purge procedure, the ethane level was analyzed by gas chromatography. Exhaled ethane levels were elevated in ILD patients (n = 34, mean +/- SD, 8.5 +/- 8.0 pmol/dL) compared with healthy volunteers (n = 16, 2.9 +/- 1.0 pmol/dL; p ethane levels were largely consistent with the clinical course. Four patients with IPF who had persistently high ethane levels died or deteriorated, whereas those with ethane levels ethane concentrations were positively correlated with levels of lactate dehydrogenase (Spearman rank correlation coefficient [rs], 0.28, p = 0.026) and C-reactive protein (rs, 0.38, p = 0.025) and were inversely correlated with Pa(O2) (rs, - 0.40, p = 0.0026). Patients showing increased uptake on (67)Ga scintigraphy demonstrated higher ethane levels (n = 19, 7.5 +/- 5.7 pmol/dL) compared with those who did not show increased uptake on scintigraphy (n = 10, 3.0 +/- 2.4 pmol/dL; p ethane is elevated in patients with ILD and is correlated with the clinical outcome, suggesting that it provides useful information about ongoing oxidative stress, and thereby disease activity and severity in ILD.

  11. Computer-based quantitative computed tomography image analysis in idiopathic pulmonary fibrosis: A mini review.

    Science.gov (United States)

    Ohkubo, Hirotsugu; Nakagawa, Hiroaki; Niimi, Akio

    2018-01-01

    Idiopathic pulmonary fibrosis (IPF) is the most common type of progressive idiopathic interstitial pneumonia in adults. Many computer-based image analysis methods of chest computed tomography (CT) used in patients with IPF include the mean CT value of the whole lungs, density histogram analysis, density mask technique, and texture classification methods. Most of these methods offer good assessment of pulmonary functions, disease progression, and mortality. Each method has merits that can be used in clinical practice. One of the texture classification methods is reported to be superior to visual CT scoring by radiologist for correlation with pulmonary function and prediction of mortality. In this mini review, we summarize the current literature on computer-based CT image analysis of IPF and discuss its limitations and several future directions. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  12. Non-small cell lung cancer: evaluation of the relationship between fibrosis and washout feature at dynamic contrast enhanced CT

    International Nuclear Information System (INIS)

    Ye Xiaodan; Yuan Zheng; Ye Jianding; Li Huimin; Zhu Yuzhao; Zhang Shunmin; Liu Shiyuan; Xiao Xiangsheng

    2010-01-01

    Objective: To correlate dynamic parameters at contrast enhanced CT and interstitial fibrosis grade of' non-small cell lung cancer (NSCLC). Methods: Twenty-nine patients with NSCLC were evaluated by multi-slice CT. Images were obtained before and at 20, 30, 45, 60, 75, 90, 120, 180, 300, 540, 720, 900 and 1200 s after the injection of contrast media, which was administered at a rate of 4 ml/s for a total of 420 mg I/kg body weight. Washout parameters were calculated. Lung cancer specimens were stained with hematoxylin-eosin stain and collagen and elastic double stain. Spearman test was made to analyze correlation between dynamic parameters and interstitial fibrosis grade of tumor. Results: Twenty- nine NSCLC demonstrated washout at 20 min 12.1 (0.32-58.0) HU, washout ratio at 20 minutes 15.3% (0.3%-39.2%), slope of washout at 20 minutes 0.0152%/s (0.0007%/s-0.0561%/s). Interstitial fibrosis of 29 lesions was graded as grade Ⅰ (10), grade Ⅱ (14) and grade Ⅲ (5). There were significant correlation between washout at 20 min (r=-0.402, P<0.05), washout ratio at 20 min (r= -0.372, P<0.05), slope of washout ratio (r=-0.459, P<0.05) and interstitial fibrosis grade in tumors. Conclusion: NSCLC washout features at dynamic multi-detector CT correlates with interstitial fibrosis in the tumor. (authors)

  13. Muc1 deficiency exacerbates pulmonary fibrosis in a mouse model of silicosis.

    Science.gov (United States)

    Kato, Kosuke; Zemskova, Marina A; Hanss, Alec D; Kim, Marianne M; Summer, Ross; Kim, Kwang Chul

    2017-11-25

    MUC1 (MUC in human and Muc in animals) is a membrane-tethered mucin expressed on the apical surface of lung epithelial cells. However, in the lungs of patients with interstitial lung disease, MUC1 is aberrantly expressed in hyperplastic alveolar type II epithelial (ATII) cells and alveolar macrophages (AM), and elevated levels of extracellular MUC1 are found in bronchoalveolar lavage (BAL) fluid and the serum of these patients. While pro-fibrotic effects of extracellular MUC1 have recently been described in cultured fibroblasts, the contribution of MUC1 to the pathobiology of pulmonary fibrosis is unknown. In this study, we hypothesized that MUC1 deficiency would reduce susceptibility to pulmonary fibrosis in a mouse model of silicosis. We employed human MUC1 transgenic mice, Muc1 deficient mice and wild-type mice on C57BL/6 background in these studies. Some mice received a one-time dose of crystalline silica instilled into their oropharynx in order to induce pulmonary fibrosis and assess the effects of Muc1 deficiency on fibrotic and inflammatory responses in the lung. As previously described in other mouse models of pulmonary fibrosis, we found that extracellular MUC1 levels were markedly increased in whole lung tissues, BALF and serum of human MUC1 transgenic mice after silica. We also detected an increase in total MUC1 levels in the lungs of these mice, indicating that production as well as release contributed to elevated levels after lung injury. Immunohistochemical staining revealed that increased MUC1 expression was mostly confined to ATII cells and AMs in areas of fibrotic remodeling, illustrating a pattern similar to the expression of MUC1 in human fibrotic lung tissues. However, contrary to our hypothesis, we found that Muc1 deficiency resulted in a worsening of fibrotic remodeling in the mouse lung as judged by an increase in number of silicotic nodules, an increase in lung collagen deposition and an increase in the severity of pulmonary inflammation

  14. Sirtuin 7 is decreased in pulmonary fibrosis and regulates the fibrotic phenotype of lung fibroblasts.

    Science.gov (United States)

    Wyman, Anne E; Noor, Zahid; Fishelevich, Rita; Lockatell, Virginia; Shah, Nirav G; Todd, Nevins W; Atamas, Sergei P

    2017-06-01

    Pulmonary fibrosis is a severe condition with no cure and limited therapeutic options. A better understanding of its pathophysiology is needed. Recent studies have suggested that pulmonary fibrosis may be driven by accelerated aging-related mechanisms. Sirtuins (SIRTs), particularly SIRT1, SIRT3, and SIRT6, are well-known mediators of aging; however, limited data exist on the contribution of sirtuins to lung fibrosis. We assessed the mRNA and protein levels of all seven known sirtuins in primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in comparison with lung fibroblasts from healthy controls. These unbiased tests revealed a tendency for all sirtuins to be expressed at lower levels in fibroblasts from patients compared with controls, but the greatest decrease was observed with SIRT7. Similarly, SIRT7 was decreased in lung tissues of bleomycin-challenged mice. Inhibition of SIRT7 with siRNA in cultured lung fibroblasts resulted in an increase in collagen and α-smooth muscle actin (α-SMA). Reciprocally, overexpression of SIRT7 resulted in lower basal and TGF-β-induced levels of COL1A1, COL1A2, COL3A1, and α-SMA mRNAs, as well as collagen and α-SMA proteins. Induced changes in SIRT7 had no effect on endogenous TGF-β mRNA levels or latent TGF-β activation, but overexpression of SIRT7 reduced the levels of Smad3 mRNA and protein. In conclusion, the decline in SIRT7 in lung fibroblasts has a profibrotic effect, which is mediated by changes in Smad3 levels.

  15. Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension.

    Science.gov (United States)

    Avouac, Jerome; Konstantinova, Irena; Guignabert, Christophe; Pezet, Sonia; Sadoine, Jeremy; Guilbert, Thomas; Cauvet, Anne; Tu, Ly; Luccarini, Jean-Michel; Junien, Jean-Louis; Broqua, Pierre; Allanore, Yannick

    2017-11-01

    To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH. Mice received two doses of IVA337 (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. IVA337 demonstrated at a dose of 100 mg/kg a marked protection from the development of lung fibrosis in both mouse models compared with mice receiving 30 mg/kg of IVA337 or vehicle. Histological score was markedly reduced by 61% in the bleomycin model and by 50% in Fra-2 transgenic mice, and total lung hydroxyproline concentrations decreased by 28% and 48%, respectively, as compared with vehicle-treated mice. IVA337 at 100 mg/kg also significantly decreased levels of fibrogenic markers in lesional lungs of both mouse models. In addition, IVA337 substantially alleviated PH in Fra-2 transgenic mice by improving haemodynamic measurements and vascular remodelling. In primary human lung fibroblasts, IVA337 inhibited in a dose-dependent manner fibroblast to myofibroblasts transition induced by TGF-β and fibroblast proliferation mediated by PDGF. We demonstrate that treatment with 100 mg/kg IVA337 prevents lung fibrosis in two complementary animal models and substantially attenuates PH in the Fra-2 mouse model. These findings confirm that the pan-PPAR agonist IVA337 is an appealing therapeutic candidate for these cardiopulmonary involvements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Disease progression in usual interstitial pneumonia compared with desquamative interstitial pneumonia. Assessment with serial CT

    International Nuclear Information System (INIS)

    Hartman, T.E.; Primack, S.L.; Kang, E.Y.

    1997-01-01

    Objective. To determine the outcome of areas of ground-glass attenuation and assess disease progression on serial high-resolution CT (HRCT) scans of patients with biopsy specimen-proved usual interstitial pneumonia (UIP) and desquamative interstitial pneumonia (DIP). Materials and methods. Twelve patients with biopsy specimen-proved UIP and 11 patients with biopsy specimen-proved DIP who had initial and follow-up HRCT scans (median interval, 10 months) were reviewed. Eleven patients with UIP and 11 with DIP received treatment between the initial and follow-up CT scans. The scans were evaluated for the presence and extent of ground-glass attenuation, irregular linear opacities and honeycombing, and overall extent of parenchymal involvement. Results. On initial CT scans, all 12 patients with UIP had areas of ground-glass attenuation (mean±SD extent, 30±16%) and irregular lines (mean±SD extent, 17±7%) and 10 patients had honeycombing (mean±SD extent, 10±6%). All 11 patients with DIP had areas of ground-glass attenuation on initial HRCT scans (mean±SD extent, 51±26%), 5 patients had irregular linear opacities (mean±SD extent, 5±5%), and 1 patient had honeycombing. Nine of the 12 patients with UIP showed increase in the extent of ground-glass attenuation (n=6) or progression to irregular lines (n=2) or honeycombing (n=4) on follow-up as compared with only 2 patients with DIP who showed progression to irregular lines (n=1) or honeycombing (n=1) (p 2 test). Conclusion. In patients with UIP, areas of ground-glass attenuation usually increase in extent or progress to fibrosis despite treatment. Areas of ground-glass attenuation in most patients with DIP remain stable or improve with treatment. (authors)

  17. Thermotransport in interstitial solid solutions

    International Nuclear Information System (INIS)

    Fogel'son, R.L.

    1982-01-01

    On the basis of literature data the problem of thermotransport of impurities (H, N, O, C) in interstitial solid solutions is considered. It is shown that from experimental data on the thermotransport an important parameter of dissolved atoms can be found which characterizes atom state in these solutions-enthalpy of transport

  18. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  19. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  20. Cystic Fibrosis (CF): Chloride Sweat Test

    Science.gov (United States)

    ... on this topic for: Parents Kids Teens Cystic Fibrosis Cystic Fibrosis and Nutrition Cystic Fibrosis (CF) Respiratory Screen: Sputum Cystic Fibrosis: Diet and Nutrition Cystic Fibrosis Cystic Fibrosis: Diet and Nutrition View more Partner Message ...

  1. Significance of connective tissue diseases features in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Vincent Cottin

    2013-09-01

    Full Text Available Interstitial lung disease (ILD can occur in any of the connective tissue diseases (CTD with varying frequency and severity, and an overall long-term prognosis that is less severe than that of idiopathic pulmonary fibrosis (IPF. Because ILD may be the presenting manifestation of CTD and/or the dominant manifestation of CTD, clinical extra-thoracic manifestations should be systematically considered in the diagnostic approach of ILD. When present, autoantibodies strongly contribute to the recognition and classification of the CTD. Patients with clinical extrathoracic manifestations of CTD and/or autoantibodies (especially with a high titer and/or the antibody is considered “highly specific” of an autoimmune condition, but who do not fit with established international CTD criteria may be called undifferentiated CTD or “lung-dominant CTD”. Although it remains to be determined which combination of symptoms and serologic tests best identify the subset of patients with clinically relevant CTD features, available evidence suggests that such patients may have distinct clinical and imaging presentation and may portend a distinct clinical course. However, autoantibodies alone when present in IPF patients do not seem to impact prognosis or management. Referral to a rheumatologist and multidisciplinary discussion may contribute to management of patients with undifferentiated CTD.

  2. Impairment of Excitation-Contraction Coupling in Right Ventricular Hypertrophied Muscle with Fibrosis Induced by Pulmonary Artery Banding.

    Directory of Open Access Journals (Sweden)

    Yoichiro Kusakari

    Full Text Available Interstitial myocardial fibrosis is one of the factors responsible for dysfunction of the heart. However, how interstitial fibrosis affects cardiac function and excitation-contraction coupling (E-C coupling has not yet been clarified. We developed an animal model of right ventricular (RV hypertrophy with fibrosis by pulmonary artery (PA banding in rats. Two, four, and six weeks after the PA-banding operation, the tension and intracellular Ca2+ concentration of RV papillary muscles were simultaneously measured (n = 33. The PA-banding rats were clearly divided into two groups by the presence or absence of apparent interstitial fibrosis in the papillary muscles: F+ or F- group, respectively. The papillary muscle diameter and size of myocytes were almost identical between F+ and F-, although the RV free wall weight was heavier in F+ than in F-. F+ papillary muscles exhibited higher stiffness, lower active tension, and lower Ca2+ responsiveness compared with Sham and F- papillary muscles. In addition, we found that the time to peak Ca2+ had the highest correlation coefficient to percent of fibrosis among other parameters, such as RV weight and active tension of papillary muscles. The phosphorylation level of troponin I in F+ was significantly higher than that in Sham and F-, which supports the idea of lower Ca2+ responsiveness in F+. We also found that connexin 43 in F+ was sparse and disorganized in the intercalated disk area where interstitial fibrosis strongly developed. In the present study, the RV papillary muscles obtained from the PA-banding rats enabled us to directly investigate the relationship between fibrosis and cardiac dysfunction, the impairment of E-C coupling in particular. Our results suggest that interstitial fibrosis worsens cardiac function due to 1 the decrease in Ca2+ responsiveness and 2 the asynchronous activation of each cardiac myocyte in the fibrotic preparation due to sparse cell-to-cell communication.

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

    Directory of Open Access Journals (Sweden)

    Juan Pablo Casas

    2008-08-01

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

  4. Role of atrial endothelial cells in the development of atrial fibrosis and fibrillation in response to pressure overload.

    Science.gov (United States)

    Kume, Osamu; Teshima, Yasushi; Abe, Ichitaro; Ikebe, Yuki; Oniki, Takahiro; Kondo, Hidekazu; Saito, Shotaro; Fukui, Akira; Yufu, Kunio; Miura, Masahiro; Shimada, Tatsuo; Takahashi, Naohiko

    Monocyte chemoattractant protein-1 (MCP-1)-mediated inflammatory mechanisms have been shown to play a crucial role in atrial fibrosis induced by pressure overload. In the present study, we investigated whether left atrial endothelial cells would quickly respond structurally and functionally to pressure overload to trigger atrial fibrosis and fibrillation. Six-week-old male Sprague-Dawley rats underwent suprarenal abdominal aortic constriction (AAC) or a sham operation. By day 3 after surgery, macrophages were observed to infiltrate into the endocardium. The expression of MCP-1 and E-selectin in atrial endothelium and the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and ED1 in left atrial tissue were enhanced. Atrial endothelial cells were irregularly hypertrophied with the disarrangement of lines of cells by scanning electron microscopy. Various-sized gap formations appeared along the border in atrial endothelial cells, and several macrophages were located just in the endothelial gap. Along with the development of heterogeneous interstitial fibrosis, interatrial conduction time was prolonged and the inducibility of atrial fibrillation by programmed extrastimuli was increased in the AAC rats compared to the sham-operated rats. Atrial endothelium responds rapidly to pressure overload by expressing adhesion molecules and MCP-1, which induce macrophage infiltration into the atrial tissues. These processes could be an initial step in the development of atrial remodeling for atrial fibrillation. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Nephrogenic systemic fibrosis

    International Nuclear Information System (INIS)

    Samtleben, W.

    2007-01-01

    A scleromyxedema-like disease was recognized in 1997. In 2000 this disorder was first published and termed nephrogenic fibrosing dermopathy because all patients had advanced renal failure. In 2006 it was discovered that the patients had a history of a preceding contrast-enhanced magnetic resonance imaging (MRI). All patients had acute or chronic severe renal insufficiency with a glomerular filtration rate (GFR) 2 . So far a total of about 215 patients with this new skin disorder have been reported to international registries. The skin thickening has a typical histology and begins in the peripheral extremities and progresses proximally, including also the abdominal wall and the head in some patients. NSF involves not only the skin, but also the muscles and other organs (e.g., lungs, heart, eyes) in some patients. Therefore the term nephrogenic systemic fibrosis (NSF) was introduced. Skin fibrosis and sclerosis are usually progressive with disabling contractures of involved joints (knees, hands, feet). NSF may be lethal in up to 28% of patients. Spontaneous remissions are rare. No generally accepted treatment is available. So far, the pathogenesis is not well understood. One hypothesis supposes a role of gadolinium liberated from the contrast agents. As patients with acute or chronic advanced renal failure (GFR 2 ) including those with hepatorenal dysfunctions are at high risk to develop NSF after exposure to gadolinium-based contrast agents, contrast-enhanced MRI should be avoided in this group and alternative diagnostic procedures should be used whenever possible. (orig.) [de

  6. Evidence for chronic inflammation as a component of the interstitial lung disease associated with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Rossi, G.A.; Bitterman, P.B.; Rennard, S.I.; Ferrans, V.J.; Crystal, R.G.

    1985-01-01

    Progressive systemic sclerosis (PSS) is a generalized disorder characterized by fibrosis of many organs including the lung parenchyma. Unlike most other interstitial disorders, traditional concepts of the interstitial lung disease associated with PSS have held it to be a ''pure'' fibrotic disorder without a significant inflammatory component. To directly evaluate whether an active alveolitis is associated with this disorder, patients with chronic interstitial lung disease and PSS were studied by open lung biopsy, gallium-67 scanning, and bronchoalveolar lavage. Histologic evaluation of the biopsies demonstrated that the interstitial fibrosis of PSS is clearly associated with the presence of macrophages, lymphocytes, and polymorphonuclear leukocytes, both in the interstitium and on the alveolar epithelial surface. Gallium-67 scans were positive in 77% of the patients, showing diffuse, primarily lower zone uptake, suggestive of active inflammation. Consistent with the histologic findings, bronchoalveolar lavage studies demonstrated a mild increase in the proportions of neutrophils and eosinophils with occasional increased numbers of lymphocytes. Importantly, alveolar macrophages from patients with PSS showed increased release of fibronectin and alveolar-macrophage-derived growth factor, mediators that together stimulate lung fibroblasts to proliferate, thus suggesting at least one mechanism modulating the lung fibrosis of these patients

  7. Detection and classification of interstitial lung diseases and emphysema using a joint morphological-fuzzy approach

    Science.gov (United States)

    Chang Chien, Kuang-Che; Fetita, Catalin; Brillet, Pierre-Yves; Prêteux, Françoise; Chang, Ruey-Feng

    2009-02-01

    Multi-detector computed tomography (MDCT) has high accuracy and specificity on volumetrically capturing serial images of the lung. It increases the capability of computerized classification for lung tissue in medical research. This paper proposes a three-dimensional (3D) automated approach based on mathematical morphology and fuzzy logic for quantifying and classifying interstitial lung diseases (ILDs) and emphysema. The proposed methodology is composed of several stages: (1) an image multi-resolution decomposition scheme based on a 3D morphological filter is used to detect and analyze the different density patterns of the lung texture. Then, (2) for each pattern in the multi-resolution decomposition, six features are computed, for which fuzzy membership functions define a probability of association with a pathology class. Finally, (3) for each pathology class, the probabilities are combined up according to the weight assigned to each membership function and two threshold values are used to decide the final class of the pattern. The proposed approach was tested on 10 MDCT cases and the classification accuracy was: emphysema: 95%, fibrosis/honeycombing: 84% and ground glass: 97%.

  8. Interstitial microwave hyperthermia treatment investigations

    International Nuclear Information System (INIS)

    Siauve, N; Lormel, C

    2012-01-01

    Microwave ablation also called interstitial hyperthermia is a medical procedure used in the treatment of many cancers, cardiac arrhythmias and other medical conditions. With this medical therapy, an electromagnetic source (antenna) is directly positioned in the target tissue and a sufficient power is injected to necrosis the tissue. The aim of this study is to propose a design procedure and develop the associated tools, for determining the optimal shape, dimensions, type and operating frequency of antenna according to the target volume. In this context, a 3D numerical predictive model of temperature elevation induced by the electric fields and two benches for thermal and electrical tissues properties characterization have been developed. To validate the procedure and the different tools, an experimental bench test which includes interstitial antenna, external microwave generator, phantom that represents the target tissue and measurement system of temperature and electric field has been elaborated.

  9. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

    Directory of Open Access Journals (Sweden)

    David Vansthertem

    2010-01-01

    Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

  10. Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis

    NARCIS (Netherlands)

    Gonzalez, Julien; Mouttalib, Sofia; Delage, Christine; Calise, Denis; Maoret, Jean-Jose; Pradere, Jean-Philippe; Klein, Julie; Buffin-Meyer, Benedicte; Van der Veen, Betty; Charo, Israel F.; Heeringa, Peter; Duchene, Johan; Bascands, Jean-Loup; Schanstra, Joost-Peter

    2013-01-01

    Most end-stage renal disease kidneys display accumulation of extracellular matrix (ECM) in the renal tubular compartment (tubular interstitial fibrosis - TIF) which is strongly correlated with the future loss of renal function. Although inflammation is a key event in the development of TIF, it can

  11. IDENTIFICATION AND CHARACTERIZATION OF AN IDIOPATHIC PULMONARY FIBROSIS-LIKE CONDITION IN CATS

    Science.gov (United States)

    Interstitial lung diseases are a heterogeneous group of disorders due to a variety of causes. In veterinary medicine, those with a prominent fibrotic component of unknown etiology are often called idiopathic pulmonary fibrosis (IPF). In human medicine, this term is reserved for ...

  12. Lysyl oxidases in idiopathic pulmonary fibrosis: A key participant in collagen I matrix remodelling

    NARCIS (Netherlands)

    Tjin, Gavin; Mahar, Annabelle; Kable, Eleanor; Burgess, Janette

    2015-01-01

    Introduction: The fibrotic element in Idiopathic Pulmonary Fibrosis (IPF) is a key feature and is associated with Usual Interstitial Pneumonia (UIP) pattern. Fibrillar collagen I (COL1) has second harmonic generation (SHG) properties, with signals both in the forward (F) (organized collagen) &

  13. Pathological and radiological correlation in an autopsy case of combined pulmonary fibrosis and emphysema

    Directory of Open Access Journals (Sweden)

    Karata H

    2015-07-01

    Full Text Available Hiroki Karata,1 Tomonori Tanaka,1 Ryoko Egashira,2 Kazuhiro Tabata,1 Kyoko Otani,3 Ryuji Hayashi,4 Takashi Hori,5 Junya Fukuoka1 1Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 2Department of Radiology, Faculty of Medicine, Saga University, Saga, Japan; 3Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan; 4Department of Internal Medicine, University of Toyama, Faculty of Medicine, Toyama, Japan; 5Laboratory of Pathology, Toyama University Hospital, Toyama, Japan Abstract: We report an educational autopsy case of combined pulmonary fibrosis and emphysema. Radiological patterns of the upper lung were considered as mostly emphysema, but pathological observation revealed significant interstitial fibrosis of usual interstitial pneumonia as a major pathology. The patient eventually developed acute exacerbation of background interstitial pneumonia. Careful radiological and pathological correlation of the current case indicates that regions with distal acinar emphysema on computed tomography image may possess histologically marked dense fibrosis of lethal interstitial pneumonia. Keywords: interstitial pneumonia, CPFE, AEF, smoking, CT

  14. Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

    Science.gov (United States)

    Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.

    2012-01-01

    A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797

  15. The Interplay between Inflammation and Fibrosis in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Irina B. Torres

    2014-01-01

    Full Text Available Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

  16. Management of suspected monogenic lung fibrosis in a specialised centre

    Directory of Open Access Journals (Sweden)

    Raphael Borie

    2017-04-01

    Full Text Available At least 10% of patients with interstitial lung disease present monogenic lung fibrosis suspected on familial aggregation of pulmonary fibrosis, specific syndromes or early age of diagnosis. Approximately 25% of families have an identified mutation in genes mostly involved in telomere homeostasis, and more rarely in surfactant homeostasis. Beyond pathophysiological knowledge, detection of these mutations has practical consequence for patients. For instance, mutations involved in telomere homeostasis are associated with haematological complications after lung transplantation and may require adapted immunosuppression. Moreover, relatives may benefit from a clinical and genetic evaluation that should be specifically managed. The field of genetics of pulmonary fibrosis has made great progress in the last 10 years, raising specific problems that should be addressed by a specialised team.

  17. Flock worker's lung: chronic interstitial lung disease in the nylon flocking industry.

    Science.gov (United States)

    Kern, D G; Crausman, R S; Durand, K T; Nayer, A; Kuhn, C

    1998-08-15

    Two young men working at a nylon flocking plant in Rhode Island developed interstitial lung disease of unknown cause. Similar clusters at the same company's Canadian plant were reported previously. To define the extent, clinicopathologic features, and potential causes of the apparent disease outbreak. Case-finding survey and retrospective cohort study. Academic occupational medicine program. All workers employed at the Rhode Island plant on or after 15 June 1990. Symptomatic employees had chest radiography, pulmonary function tests, high-resolution computed tomography, and serologic testing. Those with unexplained radiographic or pulmonary function abnormalities underwent bronchoalveolar lavage, lung biopsy, or both. The case definition of "flock worker's lung" required histologic evidence of interstitial lung disease (or lavage evidence of lung inflammation) not explained by another condition. Eight cases of flock worker's lung were identified at the Rhode Island plant. Three cases were characterized by a high proportion of eosinophils (25% to 40%) in lavage fluid. Six of the seven patients who had biopsy had histologic findings of nonspecific interstitial pneumonia, and the seventh had bronchiolitis obliterans organizing pneumonia. All seven of these patients had peribronchovascular interstitial lymphoid nodules, usually with germinal centers, and most had lymphocytic bronchiolitis and interstitial fibrosis. All improved after leaving work. Review of the Canadian tissue specimens showed many similar histologic findings. Among the 165-member study cohort, a 48-fold or greater increase was seen in the sex-adjusted incidence rate of all interstitial lung disease. Work in the nylon flocking industry poses substantial risk for a previously unrecognized occupational interstitial lung disease. Nylon fiber is the suspected cause of this condition.

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

    Science.gov (United States)

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

    2016-10-01

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

  19. Fibrosis of the pancreas: the initial tissue damage and the resulting pattern.

    Science.gov (United States)

    Klöppel, Günter; Detlefsen, Sönke; Feyerabend, Bernd

    2004-07-01

    Fibrosis in the pancreas is caused by such processes as necrosis/apoptosis, inflammation or duct obstruction. The initial event that induces fibrogenesis in the pancreas is an injury that may involve the interstitial mesenchymal cells, the duct cells and/or the acinar cells. Damage to any one of these tissue compartments of the pancreas is associated with cytokine-triggered transformation of resident fibroblasts/pancreatic stellate cells into myofibroblasts and the subsequent production and deposition of extracellular matrix. Depending on the site of injury in the pancreas and the involved tissue compartment, predominantly inter(peri)lobular fibrosis (as in alcoholic chronic pancreatitis), periductal fibrosis (as in hereditary pancreatitis), periductal and interlobular fibrosis (as in autoimmune pancreatitis) or diffuse inter- and intralobular fibrosis (as in obstructive chronic pancreatitis) develops.

  20. Lung lobar volume in patients with chronic interstitial pneumonia

    International Nuclear Information System (INIS)

    Harada, Hisao; Koba, Hiroyuki; Saitoh, Tsukasa; Abe, Shosaku.

    1997-01-01

    We measured lung lobar volume by using helical computed tomography (HCT) in 23 patients with idiopathic interstitial pneumonia (IIP), 7 patients with chronic interstitial pneumonia associated with collagen vascular disease (CVD-IP), and 5 healthy volunteers HCT scanning was done at the maximal inspiratory level and the resting end-expiratory level. To measure lung lobar volume, we traced the lobar margin on HCT images with a digitizer and calculated the lobar volume with a personal computer. The lower lobar volume and several factors influencing it in chronic interstitial pneumonia were studied. At the maximal inspiratory level, the lower lobar volume as a percent of the whole lung volume was 46.8±4.13% (mean ± SD) in the volunteers, 39.5±6.19% in the patients with IIP, and 27.7±7. 86% in the patients with CVD-IP. The lower lobar volumes in the patients were significantly lower than in the volunteers. Patients with IIP in whom autoantibody tests were positive had lower lobar volumes that were very low and were similar to those of patients with CVD-IP. These data suggest that collagen vascular disease may develop in patients with interstitial pneumonia. The patients with IIP who had emphysematous changes on the CT scans had smaller decreases in total lung capacity and lower ratios of forced expiratory volume in one second to forced vital capacity than did those who had no emphysematous changes, those two groups did not differ in the ratio of lower lobar volume to whole lung volume. This suggests that emphysematous change is not factor influencing lower lobar volume in patients with chronic interstitial pneumonia. We conclude that chronic interstitial pneumonia together with very low values for lower lobar volume may be a pulmonary manifestation of collagen vascular disease. (author)

  1. Nephrogenic systemic fibrosis.

    LENUS (Irish Health Repository)

    Kennedy, C

    2010-11-05

    Nephroaenic systemic fibrosis (NSF) is a potentiallv fatal dermatiological condition found exclusively in patients with advanced renal I failure. There is minimal literature regarding the epidemiology and outcomes of patients with NSF in Ireland. A retrospective chart review was performed for all patients with NSF in Ireland. Ireland\\'s experience with the disease was examined in light of international reports. There have been three cases of NSF in Ireland; an area which serves 1915 dialysis patients--giving a point prevalence among Irish end-stage kidney disease patients of 0.002. There was a large variation in disease severity between the three patients. All three patients had significant exposure to gadolinium chelate. Caution with gadolinium administration must be exercised in patients with advanced renal failure.

  2. The role of interstitial changes in the progression of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Beata Sulikowska

    2015-07-01

    Full Text Available Interstitium – the renal tubulointerstitial compartment – is located between the renal tubule basement membrane and microcirculation vessels. Interstitial fibroblasts produce the extracellular matrix and constitute the structure’s cellular skeleton, regulating spatial relationships between its components (microenvironment.The tubular epithelium and endothelium cooperate within an integrated microenvironment. Structural or functional impairment of the extracellular matrix, microcirculation vessels or tubular epithelium results in disturbances of tubulointerstitial compartment components.In the course of glomerular kidney diseases, the intrarenal RAA system becomes activated and inflammatory mediators are released. Interstitial inflammation and microcirculatory disorders develop, inducing adverse consequences, manifested mainly through the process of hypoxia and inflammation.Inflammation-induced increase in interleukin-1 (TNF-α expression leads to increased concentrations of VEGF, ICAM-1, angiotensin II, IL-6 and IL-8. Cytokines activate fibroblasts, myofibroblasts and endothelial cells. Fibrosis is also triggered by HIF-1alpha pathway activation, resulting in vascular growth and fibroblast proliferation. This reaction likewise occurs through activation of NF-ĸβ, EPO, GLUT-1, IGF-1 and INOS.Interstitial fibrosis is one of the factors determining the clinical course of kidney diseases. Apart from inducing fibrosis, microcirculatory disorders lead to the progression of hypoxia.Angiogenesis is a part of the repair process accompanying fibrosis. Its determinant is the normal function and structure of endothelial cells manifested by their ability to migrate and proliferate in response to, inter alia, angiopoietins, VEGF and nitric oxide synthase.Administering a three-drug RAAS-inhibiting therapy to patients with chronic glomerulopathies improves tubular function, measured by the decrease in excretion of NAG and propeptide of type III

  3. A first-principles investigation of interstitial defects in dilute tungsten alloys

    Energy Technology Data Exchange (ETDEWEB)

    Gharaee, Leili; Erhart, Paul, E-mail: erhart@chalmers.se

    2015-12-15

    The thermodynamic properties of intrinsic and extrinsic (Ti, V, Zr, Nb, Hf, Ta, Re) defects in tungsten have been investigated using density functional theory calculations. The formation energies of substitutional defects are discussed with respect to their thermodynamic solubility limits. Several different interstitial configurations have been identified as local minima on the potential energy surface. In addition to dumbbell configurations with orientations along 〈111〉 and 〈110〉, a lower symmetry configuration is described, which is referred to as a bridge interstitial. This interstitial type is found to be the lowest energy configuration for mixed-interstitials containing Ti, V, and Re, and can be up to 0.2 eV lower in energy than the other configurations. According to the calculations Ti, V and Re also trap self-interstitial atoms, which can be produced in substantial numbers during ion irradiation, affecting the mobility of the latter.

  4. Nephrogenic systemic fibrosis: epidemiology update

    DEFF Research Database (Denmark)

    Marckmann, P.

    2008-01-01

    Purpose of review The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. Recent findings Epidemiological and histochemical studies demonstrated....... Increasingly poor renal function, aberrations in calcium-phosphate metabolism and erythropoietin treatment seem to increase the risk of the disease and its severity. Up to 25-30% of patients with renal failure exposed to gadolinium-based contrast agents may develop nephrogenic systemic disease. The figure...... that gadolinium-containing contrast agents used for magnetic resonance imaging have an essential causative role in most, if not all, cases of nephrogenic systemic fibrosis. One particular agent, gadodiamide, caused the majority of cases, but gadopentetate dimeglumine has also been implicated in several cases...

  5. Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia.

    Science.gov (United States)

    Sellarés, Jacobo; Hernández-González, Fernanda; Lucena, Carmen M; Paradela, Marina; Brito-Zerón, Pilar; Prieto-González, Sergio; Benegas, Mariana; Cuerpo, Sandra; Espinosa, Gerard; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni

    2016-02-01

    Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables.We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: "presence" or "nonpresence" of bilateral Velcro crackles.Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern.In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care.

  6. Peribronchiolar fibrosis in lungs of cats chronically exposed to diesel exhaust

    International Nuclear Information System (INIS)

    Hyde, D.M.; Plopper, C.G.; Weir, A.J.; Murnane, R.D.; Warren, D.L.; Last, J.A.; Pepelko, W.E.

    1985-01-01

    This study reports the quantitative changes in the pulmonary proximal acinar region following chronic exposure to diesel exhaust and following an additional 6 months in clean air. Cats (13 months of age) from a minimum disease colony were exposed to clean air (eight cats for 27 months and nine cats for 33 months), diesel exhaust for 8 hours/day, 7 days/week (nine cats for 27 months), or diesel exhaust for 27 months followed by 6 months in clean air (10 cats). Morphologic and morphometric evaluation using light microscopy and scanning and transmission electron microscopy revealed two major exposure-related lesions in proximal acinar regions of lungs of cats: peribronchiolar fibrosis associated with significant increases in lymphocytes, fibroblasts, and interstitial macrophages containing diesel particulate-like inclusions and bronchiolar epithelial metaplasia associated with the presence of ciliated and basal cells and alveolar macrophages containing diesel particulate-like inclusions. Peribronchiolar fibrosis was greater at the end of the 6 months in clean air following exposure, whereas the bronchiolar epithelial metaplasia was most severe at the end of exposure. Following an additional 6 months in clean air the epithelium more closely resembled the control epithelial cell population. The labeling index of terminal bronchiolar epithelium was significantly increased at the end of exposure but was not significantly different from controls or exposed cats following an additional 6 months in clean air. The ultrastructural appearance of epithelial cells remained relatively unchanged following diesel exhaust exposure with the exception of diesel particulate-like inclusions

  7. Voice Disorder in Cystic Fibrosis Patients

    Science.gov (United States)

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

    2014-01-01

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

  8. Understanding the Determinants of Health-Related Quality of Life in Rheumatoid Arthritis-Associated Interstitial Lung Disease

    Science.gov (United States)

    Natalini, Jake G.; Swigris, Jeff J.; Morisset, Julie; Elicker, Brett M.; Jones, Kirk D.; Fischer, Aryeh; Collard, Harold R.; Lee, Joyce S.

    2017-01-01

    Rationale Health-related quality of life (HRQL) is impaired among patients with interstitial lung disease (ILD). Little is understood about HRQL in specific subtypes of ILD. Objectives The aim of this study was to characterize and identify clinical determinants of HRQL among patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and compare them to patients with idiopathic pulmonary fibrosis (IPF). Methods We identified patients with a diagnosis of RA-ILD and IPF from an ongoing longitudinal cohort of ILD patients. HRQL was measured at their baseline visit using the Short Form Health Survey (SF-36), versions 1 and 2. Regression models were used to characterize and understand the relationship between selected baseline clinical covariates, the physical component score (PCS) and mental component score (MCS) of the SF-36. Measurements and Main Results RA-ILD patients (n=50) were more likely to be younger and female compared to IPF patients (n=50). After controlling for age and pulmonary function, RA-ILD patients had a lower HRQL compared to IPF patients, as measured by the PCS (P=0.03), with significant differences in two of four PCS domains – bodily pain (P<0.01) and general health (P=0.01). Clinical covariates most strongly associated with a lower PCS in RA-ILD patients compared to IPF patients were the presence of joint pain or stiffness and dyspnea severity (P<0.01). Mental and emotional health, as measured by the MCS, was similar between RA-ILD and IPF patients. Conclusion The physical components of HRQL appear worse in RA-ILD patients compared to IPF patients as measured by the PCS of the SF-36. Differences in the PCS of the SF-36 can be explained in part by dyspnea severity and joint symptoms among patients with RA-ILD. PMID:28502413

  9. Molecular and cellular mechanisms of pulmonary fibrosis

    Science.gov (United States)

    2012-01-01

    Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

  10. European Cystic Fibrosis Society Standards of Care

    DEFF Research Database (Denmark)

    Stern, Martin; Bertrand, Dominique Pougheon; Bignamini, Elisabetta

    2014-01-01

    Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful ...... to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons.......Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful...... therapies, approaches to care and indeed data recording. The quality of care for individuals with CF has become a focus at several levels: patient, centre, regional, national and international. This paper reviews the quality management and improvement issues at each of these levels with particular reference...

  11. 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 ...

  12. Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction.

    Directory of Open Access Journals (Sweden)

    Wilco P Pulskens

    Full Text Available Progressive renal disease is characterized by tubulo-interstitial injury with ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these pathophysiological processes through its canonical effects in cytokine maturation. Nlrp3 may additionally exert inflammasome-independent effects following tissue injury. Hence, in this study we investigated potential non-canonical effects of Nlrp3 following progressive renal injury by subjecting WT and Nlrp3-deficient (-/- mice to unilateral ureter obstruction (UUO. Our results revealed a progressive increase of renal Nlrp3 mRNA in WT mice following UUO. The absence of Nlrp3 resulted in enhanced tubular injury and dilatation and an elevated expression of injury biomarker NGAL after UUO. Moreover, interstitial edema was significantly elevated in Nlrp3-/- mice. This could be explained by increased intratubular pressure and an enhanced tubular and vascular permeability. In accordance, renal vascular leakage was elevated in Nlrp3-/- mice that associated with reduced mRNA expression of intercellular junction components. The decreased epithelial barrier function in Nlrp3-/- mice was not associated with increased apoptosis and/or proliferation of renal epithelial cells. Nlrp3 deficiency did not affect renal fibrosis or inflammation. Together, our data reveal a novel non-canonical effect of Nlrp3 in preserving renal integrity and protection against early tubular injury and interstitial edema following progressive renal injury.

  13. Investigations of lymphatic drainage from the interstitial space

    Science.gov (United States)

    Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration

    2017-11-01

    The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.

  14. Tumor interstitial fluid - a treasure trove of cancer biomarkers.

    Science.gov (United States)

    Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J; Timmermans-Wielenga, Vera; Talman, Mai-Lis; Serizawa, Reza R; Moreira, José M A

    2013-11-01

    Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical secretion, non-classical secretion, secretion via exosomes and membrane protein shedding. Consequently, the interstitial aqueous phase of solid tumors is a highly promising resource for the discovery of molecules associated with pathological changes in tissues. Firstly, it allows one to delve deeper into the regulatory mechanisms and functions of secretion-related processes in tumor development. Secondly, the anomalous secretion of molecules that is innate to tumors and the tumor microenvironment, being associated with cancer progression, offers a valuable source for biomarker discovery and possible targets for therapeutic intervention. Here we provide an overview of the features of tumor-associated interstitial fluids, based on recent and updated information obtained mainly from our studies of breast cancer. Data from the study of interstitial fluids recovered from several other types of cancer are also discussed. This article is a part of a Special Issue entitled: The Updated Secretome. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Imaging pulmonary fibrosis

    International Nuclear Information System (INIS)

    Brauner, M.W.; Rety, F.; Naccache, J.M.; Girard, F.; Valeyre, D.F.

    2001-01-01

    Localized fibrosis of the lung is usually scar tissue while diffuse pulmonary fibrosis is more often a sign of active disease. Chronic infiltrative lung disease may be classified into four categories: idiopathic pneumonitis, collagen diseases, granulomatosis (sarcoidosis), and caused by known diseases (pneumoconiosis, hypersensitivity pneumonitis, drug-induced lung disease, radiation). (authors)

  16. Angiogenesis in liver fibrosis

    NARCIS (Netherlands)

    Adlia, Amirah

    2017-01-01

    Angiogenesis emerges in parallel with liver fibrosis, but it is still unclear whether angiogenesis is a defense mechanism of the body in response to fibrosis, or whether it aggravates the fibrotic condition. In this thesis, Amirah Adlia applied different approaches to elucidate the role of

  17. Fibrosis and Cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R.; Erler, Janine T.

    2016-01-01

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

  18. 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

  19. Improved pulmonary function following pirfenidone treatment in a patient with progressive interstitial lung disease associated with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Zarir F Udwadia

    2015-01-01

    Full Text Available Pirfenidone is an anti-fibrotic drug which has been approved for the management of patients with Idiopathic Pulmonary Fibrosis (IPF. However, its role in interstitial lung disease (ILD due to other causes such as systemic sclerosis (SSc is not clear. We present a case of a patient with SSc associated ILD who showed a subjective as well as objective improvement in lung function with pirfenidone.

  20. Lung adenocarcinoma mimicking pulmonary fibrosis-a case report

    International Nuclear Information System (INIS)

    Mehić, Bakir; Duranović Rayan, Lina; Bilalović, Nurija; Dohranović Tafro, Danina; Pilav, Ilijaz

    2016-01-01

    Lung cancer is usually presented with cough, dyspnea, pain and weight loss, which is overlapping with symptoms of other lung diseases such as pulmonary fibrosis. Pulmonary fibrosis shows characteristic reticular and nodular pattern, while lung cancers are mostly presented with infiltrative mass, thick-walled cavitations or a solitary nodule with spiculated borders. If the diagnosis is established based on clinical symptoms and CT findings, it would be a misapprehension. We report a case of lung adenocarcinoma whose symptoms as well as clinical images overlapped strongly with pulmonary fibrosis. The patient’s non-productive cough, progressive dyspnea, restrictive pattern of pulmonary function test and CT scans (showing reticular interstitial opacities) were all indicative of pulmonary fibrosis. The patient underwent a treatment consisting of corticosteroids and antibiotics, to no avail. Histopathology of the lung showed that the patient suffered from mucinous adenocarcinoma. Albeit the immunohistochemical staining was not consistent with lung adenocarcinoma, tumor’s morphological characteristics were consistent, and were used to make the definitive diagnosis. Given the fact that radiography cannot always make a clear-cut difference between pulmonary fibrosis and lung adenocarcinomas, and that clinical symptoms often overlap, histological examination should be considered as gold standard for diagnosis of lung adenocarcinoma

  1. The interstitial pneumonitis induced by cytostatics

    International Nuclear Information System (INIS)

    Dubrava, M.; Markova, I.; Mistina, L.

    1998-01-01

    The author presents a cause of 9-year old boy with ALL-F2B in the stage of the prevention treatment where in the its course the induced interstitial pneumonitis by cytostatics was developed. The bacterial, virus, mycological and parasitic causes of the interstitial pneumonitis on the basis of the bronchoscopy, BAL, CT, scintigraphy, laboratory and by cultivation were excluded. (authors)

  2. The behavior of interstitials in irradiated graphite

    International Nuclear Information System (INIS)

    Pedraza, D.F.

    1991-01-01

    A computer model is developed to simulate the behavior of self-interstitials with particular attention to clustering. Owing to the layer structure of graphite, atomistic simulations can be performed using a large parallelepipedic supercell containing a few layers. In particular, interstitial clustering is studied here using a supercell that contains two basal planes only. Frenkel pairs are randomly produced. Interstitials are placed at sites between the crystal planes while vacancies are distributed in the two crystal planes. The size of the computational cell is 20000 atoms and periodic boundary conditions are used in two dimensions. Vacancies are assumed immobile whereas interstitials are given a certain mobility. Two point defect sinks are considered, direct recombination of Frenkel pairs and interstitial clusters. The clusters are assumed to be mobile up to a certain size where they are presumed to become loop nuclei. Clusters can shrink by emission of singly bonded interstitials or by recombination of a peripheral interstitial with a neighboring vacancy. The conditions under which interstitial clustering occurs are reported. It is shown that when clustering occurs the cluster size population gradually shifts towards the largest size cluster. The implications of the present results for irradiation growth and irradiation-induced amorphization are discussed

  3. Automatic liver volume segmentation and fibrosis classification

    Science.gov (United States)

    Bal, Evgeny; Klang, Eyal; Amitai, Michal; Greenspan, Hayit

    2018-02-01

    In this work, we present an automatic method for liver segmentation and fibrosis classification in liver computed-tomography (CT) portal phase scans. The input is a full abdomen CT scan with an unknown number of slices, and the output is a liver volume segmentation mask and a fibrosis grade. A multi-stage analysis scheme is applied to each scan, including: volume segmentation, texture features extraction and SVM based classification. Data contains portal phase CT examinations from 80 patients, taken with different scanners. Each examination has a matching Fibroscan grade. The dataset was subdivided into two groups: first group contains healthy cases and mild fibrosis, second group contains moderate fibrosis, severe fibrosis and cirrhosis. Using our automated algorithm, we achieved an average dice index of 0.93 ± 0.05 for segmentation and a sensitivity of 0.92 and specificity of 0.81for classification. To the best of our knowledge, this is a first end to end automatic framework for liver fibrosis classification; an approach that, once validated, can have a great potential value in the clinic.

  4. Chlorambucil-Induced Acute Interstitial Pneumonitis

    Directory of Open Access Journals (Sweden)

    Hammad Shafqat

    2014-01-01

    Full Text Available Chlorambucil is an alkylating agent commonly used in treatment of chronic lymphocytic leukemia (CLL. We report a case of interstitial pneumonitis developing in an 83-year-old man 1.5 months after completing a six-month course of chlorambucil for CLL. The interstitial pneumonitis responded to therapy with prednisone. We performed a systematic review of literature and identified 13 other case reports of chlorambucil-induced pulmonary toxicity, particularly interstitial pneumonitis. No unifying risk factor could be discerned and the mechanism of injury remains unknown. In contrast, major randomized trials of chlorambucil therapy in CLL have not reported interstitial pneumonitis as an adverse effect, which may be due to the rarity of the phenomenon or due to underreporting of events occurring after completion of treatment. Clinicians should consider drug-induced interstitial pneumonitis in the differential diagnosis of a suggestive syndrome developing even after discontinuation of chlorambucil.

  5. 020. Coexistence of lung adenocarcinoma and usual interstitial pneumonia: a case report

    Science.gov (United States)

    Baliaka, Aggeliki; Papaemmanouil, Styliani; Spyratos, Dionysis; Zarogoulidis, Paul; Sakkas, Leonidas

    2015-01-01

    Background Usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause. The most common symptoms are progressively increased shortness of breath and dry cough. Some studies suggest an association between usual interstitial pneumonia and lung cancer through different pathogenetic mechanisms. Objective The case presentation of a patient with lung adenocarcinoma and UIP. Methods A 66-year-old male presented with persistent dry cough, hemoptysis and dyspnea. The chest radiographs revealed a mass in the lower lobe of the left lung, measuring 3 cm, as well as diffuse interstitial changes in the same lobe. Two partial lobectomies were performed. Results Histological examination of the mass showed moderately differentiated adenocarcinoma, focally with bronchoalveolar pattern (Immunohistochemical detection of EGFR: positive). The rest lung parenchyma presented histological appearance of UIP. Conclusions According to clinicopathological studies, the prevalence of lung cancer among patients with UIP/IPF varies between 4% and 9%. The overall median survival of IPF-Ca patients is seven months in comparison with IPF only patients (14 months).

  6. Fell-Muir lecture: connective tissue growth factor (CCN2) – a pernicious and pleiotropic player in the development of kidney fibrosis

    Science.gov (United States)

    Mason, Roger M

    2013-01-01

    Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis. PMID:23110747

  7. Postoperative interstitial radiotherapy of keloids

    International Nuclear Information System (INIS)

    Clavere, P.; Bonnafoux-Clavere, A.; Roullet, B.; Morzel, A.; Rhein, B.; Bonnetblanc, J.M.; Olivier, J.P.

    1993-01-01

    During an 8-year period, 21 patients with keloids (27 keloids) were treated with keloidectomy and post-operative interstitial radiotherapy by an iridium 192 wire. Only one patient had been previously treated by corticoids, without results. A dose of 12 Gy (three patients) to 15 Gy (18 patients) was delivered at a point 2.5 mm from the axis of the wire. The follow-up time was from 2 - 104 months. The success rate, at 7 months, was close to 88%. Ao recurrence occurred in three patients without relation to the method used, the lesion-age or the localization of the lesions. There were no side-effects. This method represents an effective, non-constraining and safe treatment for keloids if the contra-indications are respected

  8. Navigation system for interstitial brachytherapy

    International Nuclear Information System (INIS)

    Strassmann, G.; Kolotas, C.; Heyd, R.

    2000-01-01

    The purpose of the stud was to develop a computed tomography (CT) based electromagnetic navigation system for interstitial brachytherapy. This is especially designed for situations when needles have to be positioned adjacent to or within critical anatomical structures. In such instances interactive 3D visualisation of the needle positions is essential. The material consisted of a Polhemus electromagnetic 3D digitizer, a Pentium 200 MHz laptop and a voice recognition for continuous speech. In addition, we developed an external reference system constructed of Perspex which could be positioned above the tumour region and attached to the patient using a non-invasive fixation method. A specially designed needle holder and patient bed were also developed. Measurements were made on a series of phantoms in order to study the efficacy and accuracy of the navigation system. The mean navigation accuracy of positioning the 20.0 cm length metallic needles within the phantoms was in the range 2.0-4.1 mm with a maximum of 5.4 mm. This is an improvement on the accuracy of a CT-guided technique which was in the range 6.1-11.3 mm with a maximum of 19.4 mm. The mean reconstruction accuracy of the implant geometry was 3.2 mm within a non-ferromagnetic environment. We found that although the needles were metallic this did not have a significant influence. We also found for our experimental setups that the CT table and operation table non-ferromagnetic parts had no significant influence on the navigation accuracy. This navigation system will be a very useful clinical tool for interstitial brachytherapy applications, particularly when critical structures have to be avoided. It also should provide a significant improvement on our existing technique

  9. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.

    Science.gov (United States)

    Newton, Chad A; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig S; Aravena, Carlos; Meyer, Keith; Raghu, Ganesh; Collard, Harold R; Garcia, Christine Kim

    2016-12-01

    Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals.115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed.Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year -1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis.Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive. Copyright ©ERS 2016.

  10. Chylothorax in dermatomyositis complicated with interstitial pneumonia.

    Science.gov (United States)

    Isoda, Kentaro; Kiboshi, Takao; Shoda, Takeshi

    2017-04-01

    Chylothorax is a disease in which chyle leaks and accumulates in the thoracic cavity. Interstitial pneumonia and pneumomediastinum are common thoracic manifestations of dermatomyositis, but chylothorax complicated with dermatomyositis is not reported. We report a case of dermatomyositis with interstitial pneumonia complicated by chylothorax. A 77-year-old woman was diagnosed as dermatomyositis with Gottron's papules, skin ulcers, anti-MDA5 antibody and rapid progressive interstitial pneumonia. Treatment with betamethasone, tacrolimus and intravenous high-dose cyclophosphamide was initiated, and her skin symptoms and interstitial pneumonia improved once. However, right-sided chylothorax began to accumulate and gradually increase, and at the same time, her interstitial pneumonia began to exacerbate, and skin ulcers began to reappear on her fingers and auricles. Although her chylothorax improved by fasting and parenteral nutrition, she died due to further exacerbations of dermatomyositis and interstitial pneumonia in spite of steroid pulse therapy, increase in the betamethasone dosage, additional intravenous high-dose cyclophosphamide and plasma pheresis. An autopsy showed no lesions such as malignant tumors in the thoracic cavity. This is the first report of chylothorax complicated by dermatomyositis with interstitial pneumonia.

  11. Unilateral lung transplantation for pulmonary fibrosis.

    Science.gov (United States)

    1986-05-01

    Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

  12. Fibrocytes in pulmonary fibrosis: a brief synopsis

    Directory of Open Access Journals (Sweden)

    Shyam Maharaj

    2013-12-01

    Full Text Available Fibrocytes are bone marrow-derived, circulating mesenchymal progenitor cells that play a role in several fibrotic disorders, including lung fibrosis. They are attracted to injured tissue by various chemokines. It is likely that fibrocytes play a detrimental role in tissue homeostasis and promote fibrosis, although this paradigm needs further confirmation. This would make fibrocytes a possible novel treatment target for fibrotic disorders. Fibrocytes also have some potential as a biomarker for idiopathic pulmonary fibrosis (IPF and other diseases, but the promising preliminary data from single centre studies still require independent validation. Despite several, as yet, unresolved issues, it has become clear that fibrocytes are more than an incidental finding in lung injury and repair, and may hold great promise for the future of IPF management.

  13. MFAP4: a candidate biomarker for hepatic and pulmonary fibrosis?

    Science.gov (United States)

    Mölleken, Christian; Poschmann, Gereon; Bonella, Francesco; Costabel, Ulrich; Sitek, Barbara; Stühler, Kai; Meyer, Helmut E; Schmiegel, Wolff H; Marcussen, Niels; Helmer, Michael; Nielsen, Ole; Hansen, Søren; Schlosser, Anders; Holmskov, Uffe; Sorensen, Grith Lykke

    2016-03-29

    Several comparable mechanisms have been identified for hepatic and pulmonary fibrosis. The human microfibrillar associated glycoprotein 4 (MFAP4), produced by activated myofibroblasts, is a ubiquitous protein playing a potential role in extracellular matrix (ECM) turnover and was recently identified as biomarker for hepatic fibrosis in hepatitis C patients. The current study aimed to evaluate serum levels of MFAP4 in patients with pulmonary fibrosis in order to test its potential as biomarker in clinical practice. A further aim was to determine whether MFAP4 deficiency in mice affects the formation of pulmonary fibrosis in the bleomycin model of lung fibrosis. 91 patients with idiopathic pulmonary fibrosis (IPF), 23 with hypersensitivity pneumonitis (HP) and 31 healthy subjects were studied. In the mouse model, C57BL/6 Mfap4+/+ and Mfap4-/- mice between 6-8 weeks of age were studied. Serum levels of MFAP4 were measured by ELISA in patients and in mice. Surfactant protein D (SP-D) and LDH were measured as comparison biomarkers in patients with pulmonary fibrosis. Morphometric assessment and the Sircol kit were used to determine the amount of collagen in the lung tissue in the mouse model. Serum levels of MFAP4 were not elevated in lung fibrosis - neither in the patients with IPF or HP nor in the animal model. Furthermore no significant correlations with pulmonary function tests of IPF patients could be found for MFAP4. MFAP4 levels were increased in BAL of bleomycin treated mice with pulmonary fibrosis. MFAP4 is not elevated in sera of patients with pulmonary fibrosis or bleomycin treated mice with pulmonary fibrosis. This may be due to different pathogenic mechanisms of liver and lung fibrogenesis. MFAP4 seems to be useful as serum biomarker for hepatic but not for lung fibrosis.

  14. HRCT of diffuse interstitial pneumonia during treatment

    International Nuclear Information System (INIS)

    Takahashi, Masashi; Sano, Akira; Imanaka, Kazufumi

    1989-01-01

    HRCT was carried out in twenty patients with diffuse interstitial pneumonia: 13 cases of IIP, 3 of BOOP, 2 of drug-induced pneumonia, 1 of rheumatoid lung and acute interstitial pneumonia of unknown origin. With special attention to inflammatory activity, the patients underwent HRCT periodically during the treatment. Correlative investigation between HRCT image and grade of accumulation in 67 Ga scintigraphy was also performed. Response to steroid therapy was clearly reflected on HRCT image, that was shown as decreasing pulmonary density or thinning of honeycomb wall. HRCT is considered to be useful in assessing the activity of diffuse interstitial pneumonia. (author)

  15. Percepção da gravidade da doença em pacientes adultos com fibrose cística Perception of disease severity in adult patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Paulo de Tarso Roth Dalcin

    2009-01-01

    Full Text Available OBJETIVO: Avaliar a percepção da gravidade da doença em pacientes com fibrose cística (FC, investigando sua relação com escore clínico, escore radiológico, testes de função pulmonar, adesão ao tratamento e percepção de autocuidado. MÉTODOS: Estudo transversal, prospectivo, envolvendo pacientes com FC atendidos em um programa para adultos com FC. A percepção da gravidade da doença, a adesão ao tratamento e o relato de autocuidado foram avaliados por questionários. Foram obtidos de todos os pacientes dados clínicos, escore clínico de Shwachman-Kulczycki, escore radiológico de Brasfield e espirometria. RESULTADOS: De 38 pacientes estudados, 3 (7,9% relataram percepção de sua saúde como muito abaixo da média; 5 (13,2%, como abaixo da média; 15 (39,5%, como na média; 10 (26.3%, como acima da média; e 5 (13,2%, como muito acima da média. A percepção da gravidade da doença correlacionou-se significativamente com o escore clínico (r = 0,43, p = 0,007, CVF (r = 0,34, p = 0,034, VEF1 (r = 0,38, p = 0,019 e com relato de autocuidado (r = 0,33, p = 0,044, mas não com o grau de adesão (r = -0,03, p = 0,842 e escore radiológico (r = 0,33, p = 0,51. CONCLUSÕES: A percepção da gravidade da doença se relacionou com medidas objetivas de gravidade da doença (escore clínico e testes de função pulmonar e com relato de autocuidado, mas não com a adesão ao tratamento.OBJECTIVE: To evaluate the perception of disease severity in patients with cystic fibrosis (CF, investigating its relationship with clinical score, radiographic score, respiratory function tests, adherence to treatment and perception of self-care practices. METHODS: Prospective, cross-sectional study involving CF patients treated in a program for adults with CF. The perception of disease severity, adherence to treatment and reported self-care practices were evaluated by means of questionnaires. Clinical data, Shwachman-Kulczycki clinical score, Brasfield

  16. Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema.

    Science.gov (United States)

    Sato, Suguru; Tanino, Yoshinori; Misa, Kenichi; Fukuhara, Naoko; Nikaido, Takefumi; Uematsu, Manabu; Fukuhara, Atsuro; Wang, Xintao; Ishida, Takashi; Munakata, Mitsuru

    2016-01-01

    Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis.

  17. Serial high resolution CT in non-specific interstitial pneumonia: prognostic value of the initial pattern

    Energy Technology Data Exchange (ETDEWEB)

    Screaton, N.J. [Department of Radiology, Addenbrooke' s Hospital, Cambridge (United Kingdom)]. E-mail: nicholas.screaton@papworth.nhs.uk; Hiorns, M.P. [Department of Radiology, Great Ormond Street Hospital, London (United Kingdom); Lee, K.S. [Samsung Medical Centre, Seoul (Korea); Franquet, T. [Hospital de Saint Pau, Universidad Autonoma de Barcelona, Barcelona (Spain); Johkoh, T. [Department of Medical Physics and Radiology, Osaka University Graduate School of Medicine, Osaka (Japan); Fujimoto, K. [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Ichikado, K. [First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto (Japan); Colby, T.V. [Department of Laboratory Medicine/Pathology, Mayo Clinic Scottsdale, AZ (United States); Mueller, N.L. [Department of Radiology, Vancouver General Hospital, Vancouver (Canada)

    2005-01-01

    AIM: To assess the relationship between initial CT pattern and serial changes in CT findings and pulmonary function tests (PFTs) in patients with non-specific interstitial pneumonia (NSIP). MATERIALS AND METHODS: Serial high resolution (HR) CTs and PFTs were retrospectively analyzed in 38 cases of histologically proven NSIP, including 4 with cellular NSIP, 13 with mixed cellular and fibrotic NSIP, and 21 with fibrotic NSIP. The presence and extent of various CT findings were assessed. A fibrosis index (defined as the ratio of the extent of a reticular/honeycomb pattern to the overall extent of abnormal parenchyma) was derived. RESULTS: The predominant CT pattern was reticular/honeycomb in 27 (84%) cases and ground-glass/consolidation in 6 (16%) cases. Between scans, mean disease extent reduced by 5.2%. Disease extent reduced by >10% in 13 (34%) and increased by >10% in 6 (16%) patients. Histopathological subtype of NSIP did not correlate with individual CT pattern, predominant pattern, fibrosis index or serial change in disease extent on CT or PFTs. Response on follow-up CT was associated with fibrosis index, predominant pattern and extent of consolidation on initial CT. CONCLUSION: In NSIP disease, progression on CT correlates with the predominant CT pattern, fibrosis index, and extent of consolidation but not with histopathological subtype. An inflammatory (ground-glass/consolidation) predominant pattern is associated with better outcome in terms of disease extent on HRCT.

  18. ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers.

    Directory of Open Access Journals (Sweden)

    David Gonzalez

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα, Tcf4 and α-smooth muscle actin (α-SMA levels are augmented in the skeletal muscle of symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs, which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases.

  19. Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

    Science.gov (United States)

    Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

    2018-01-03

    Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non

  20. Rheumatoid arthritis-associated interstitial lung disease: lung inflammation evaluated with high resolution computed tomography scan is correlated to rheumatoid arthritis disease activity.

    Science.gov (United States)

    Pérez-Dórame, Renzo; Mejía, Mayra; Mateos-Toledo, Heidegger; Rojas-Serrano, Jorge

    2015-01-01

    To describe the association between rheumatoid arthritis disease activity (RA) and interstitial lung damage (inflammation and fibrosis), in a group of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). A retrospective study of RA patients with interstitial lung disease (restrictive pattern in lung function tests and evidence of interstitial lung disease in high resolution computed tomography (HRCT)). Patients were evaluated to exclude other causes of pulmonary disease. RA disease activity was measured with the CDAI index. Interstitial lung inflammation and fibrosis were determined by Kazerooni scale. We compared Kazerooni ground-glass score with the nearest CDAI score to HRCT date scan of the first medical evaluation at our institution. In nine patients, we compared the first ground-glass score with a second one after treatment with DMARDs and corticosteroids. Spearman's rank correlation coefficient was used to evaluate association between RA disease activity and the Kazerooni ground-glass and fibrosis scores. Thirty-four patients were included. A positive correlation between CDAI and ground-glass scores was found (rs=0.3767, P<0.028). Fibrosis and CDAI scores were not associated (rs=-0.0747, P<0.6745). After treatment, a downward tendency in the ground-glass score was observed (median [IQR]): (2.33 [2,3] vs. 2 [1.33-2.16]), P<0.056, along with a lesser CDAI score (27 [8-43] vs. 9 [5-12]), P<0.063. There is a correlation between RA disease activity and ground-glass appearance in the HRCT of RA-ILD patients. These results suggest a positive association between RA disease activity and lung inflammation in RA-ILD. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  1. Automated diagnosis of interstitial lung diseases and emphysema in MDCT imaging

    Science.gov (United States)

    Fetita, Catalin; Chang Chien, Kuang-Che; Brillet, Pierre-Yves; Prêteux, Françoise

    2007-09-01

    Diffuse lung diseases (DLD) include a heterogeneous group of non-neoplasic disease resulting from damage to the lung parenchyma by varying patterns of inflammation. Characterization and quantification of DLD severity using MDCT, mainly in interstitial lung diseases and emphysema, is an important issue in clinical research for the evaluation of new therapies. This paper develops a 3D automated approach for detection and diagnosis of diffuse lung diseases such as fibrosis/honeycombing, ground glass and emphysema. The proposed methodology combines multi-resolution 3D morphological filtering (exploiting the sup-constrained connection cost operator) and graph-based classification for a full characterization of the parenchymal tissue. The morphological filtering performs a multi-level segmentation of the low- and medium-attenuated lung regions as well as their classification with respect to a granularity criterion (multi-resolution analysis). The original intensity range of the CT data volume is thus reduced in the segmented data to a number of levels equal to the resolution depth used (generally ten levels). The specificity of such morphological filtering is to extract tissue patterns locally contrasting with their neighborhood and of size inferior to the resolution depth, while preserving their original shape. A multi-valued hierarchical graph describing the segmentation result is built-up according to the resolution level and the adjacency of the different segmented components. The graph nodes are then enriched with the textural information carried out by their associated components. A graph analysis-reorganization based on the nodes attributes delivers the final classification of the lung parenchyma in normal and ILD/emphysematous regions. It also makes possible to discriminate between different types, or development stages, among the same class of diseases.

  2. The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial.

    Science.gov (United States)

    Dowman, Leona M; McDonald, Christine F; Hill, Catherine J; Lee, Annemarie L; Barker, Kathryn; Boote, Claire; Glaspole, Ian; Goh, Nicole S L; Southcott, Anne M; Burge, Angela T; Gillies, Rebecca; Martin, Alicia; Holland, Anne E

    2017-07-01

    Uncertainty exists regarding the clinical relevance of exercise training across the range of interstitial lung diseases (ILDs). To establish the impact of exercise training in patients with ILDs of differing aetiology and severity. 142 participants with ILD (61 idiopathic pulmonary fibrosis (IPF), 22 asbestosis, 23 connective tissue disease-related ILD (CTD-ILD) and 36 with other aetiologies) were randomised to either 8 weeks of supervised exercise training or usual care. Six-minute walk distance (6MWD), Chronic Respiratory Disease Questionnaire (CRDQ), St George Respiratory Questionnaire IPF-specific version (SGRQ-I) and modified Medical Research Council dyspnoea score were measured at baseline, 9 weeks and 6 months. Exercise training significantly increased 6MWD (25 m, 95% CI 2 to 47 m) and health-related quality of life (CRDQ and SGRQ-I) in people with ILD. Larger improvements in 6MWD, CRDQ, SGRQ-I and dyspnoea occurred in asbestosis and IPF compared with CTD-ILD, but with few significant differences between subgroups. Benefits declined at 6 months except in CTD-ILD. Lower baseline 6MWD and worse baseline symptoms were associated with greater benefit in 6MWD and symptoms following training. Greater gains were seen in those whose exercise prescription was successfully progressed according to the protocol. At 6 months, sustained improvements in 6MWD and symptoms were associated with better baseline lung function and less pulmonary hypertension. Exercise training is effective in patients across the range of ILDs, with clinically meaningful benefits in asbestosis and IPF. Successful exercise progression maximises improvements and sustained treatment effects favour those with milder disease. Results, ACTRN12611000416998. 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/.

  3. Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease.

    Science.gov (United States)

    Hara, Yu; Shinkai, Masaharu; Kanoh, Soichiro; Fujikura, Yuji; K Rubin, Bruce; Kawana, Akihiko; Kaneko, Takeshi

    2017-01-01

    Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 ( 67 Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67 Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.

  4. Gastroesophageal Reflux and Idiopathic Pulmonary Fibrosis: A Review

    Directory of Open Access Journals (Sweden)

    Ahmed Fahim

    2011-01-01

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

  5. Clearance of technetium-99m-DTPA and HRCT findings in the evaluation of patients with Idiopathic Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Karkavitsas Nikolaos

    2006-02-01

    Full Text Available Abstract Background Clearance of inhaled technetium-labeled diethylenetriamine pentaacetate (99mTc-DTPA is a marker of epithelial damage and an index of lung epithelial permeability. The aim of this study was to investigate the role of 99mTc-DTPA scan in patients with Idiopathic Pulmonary Fibrosis (IPF. Our hypothesis is that the rate of pulmonary 99mTc-DTPA clearance could be associated with extent of High Resolution Computed Tomography (HRCT abnormalities, cell differential of bronchoalveolar lavage fluid (BALF and pulmonary function tests (PFTs in patients with IPF. Methods We studied prospectively 18 patients (14 male, 4 female of median age 67yr (range 55–81 with histologically proven IPF. HRCT scoring included the mean values of extent of disease. Mean values of these percentages represented the Total Interstitial Disease Score (TID. DTPA clearance was analyzed according to a dynamic study using a Venticis II radioaerosol delivery system. Results The mean (SD TID score was 36 ± 12%, 3 patients had mild, 11 moderate and 4 severe TID. Abnormal DTPA clearance half-time (t1/2 Conclusion Our data suggest that 99mTc-DTPA lung scan is not well associated with HRCT abnormalities, PFTs, and BALF cellularity in patients with IPF. Further studies in large scale of patients are needed to define the role of this technique in pulmonary fibrosis.

  6. Interstitial Metabolic Monitoring During Hemorrhagic Shock

    National Research Council Canada - National Science Library

    Pamnani, Motilal

    2004-01-01

    .... We hypothesize that decompensation results from potassium-mediated vasodilation and/or loss of cardiac contractility, and thus a method of measuring interstitial potassium should be a crucial part...

  7. Interstitial meiofauna of Namib sandy beaches

    African Journals Online (AJOL)

    1988-03-16

    Mar 16, 1988 ... Zoology Department, Institute for Coastal Research, University of Port Elizabeth, P.O. Box ... Oliff, Gardner, Turner & Sharp (1970) and later Dye, ... Wooldridge, Dye & ...... potential sources of food for interstitial organisms,.

  8. Pulmonary fibrosis and exposure to steel welding fume.

    Science.gov (United States)

    Cosgrove, M P

    2015-12-01

    Arc welders who have been exposed to high concentrations of steel welding fume for prolonged periods of time may develop pulmonary fibrosis but the nature of the fibrotic changes has been debated over the last 80 years without any clear international consensus. To characterize the nature of the pulmonary fibrosis that develops in response to steel welding fume exposure and to provide a working hypothesis that would explain the findings of the existing research, to provide a platform for future research and to inform future occupational and clinical management of welders with pulmonary effects from welding fume. Review of the world literature on pulmonary fibrosis and welding of steel in all languages using PubMed, with further secondary search of references in the articles found in the primary search. Google and Reference Manager were used as further confirmatory search tools. Only case series and case reports were found but these provided consistent evidence that the consequence of exposure to steel welding fume at high levels for a prolonged period of time is a type of pulmonary fibrosis similar to, and possibly the same as, respiratory bronchiolitis which eventually develops into desquamative interstitial pneumonia with ongoing exposure. Steel welding fume may cause an occupational respiratory bronchiolitis which may develop into de squamative interstitial pneumonia with ongoing exposure. This concept may explain the difficulties in interpreting the wider literature on welding fume and lung function at lower exposures and may also explain the increased risk of lung cancer in welders. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis

    Science.gov (United States)

    Sharma, Amit; Khan, Md. Abdul Hye; Levick, Scott P.; Lee, Kin Sing Stephen; Hammock, Bruce D.; Imig, John D.

    2016-01-01

    Cytochrome P450 (CYP) monooxygenases epoxidize the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid into novel epoxydocosapentaenoic acids (EDPs) that have multiple biological actions. The present study determined the ability of the most abundant EDP regioisomer, 19,20-EDP to reduce kidney injury in an experimental unilateral ureteral obstruction (UUO) renal fibrosis mouse model. Mice with UUO developed kidney tubular injury and interstitial fibrosis. UUO mice had elevated kidney hydroxyproline content and five-times greater collagen positive fibrotic area than sham control mice. 19,20-EDP treatment to UUO mice for 10 days reduced renal fibrosis with a 40%–50% reduction in collagen positive area and hydroxyproline content. There was a six-fold increase in kidney α-smooth muscle actin (α-SMA) positive area in UUO mice compared to sham control mice, and 19,20-EDP treatment to UUO mice decreased α-SMA immunopositive area by 60%. UUO mice demonstrated renal epithelial-to-mesenchymal transition (EMT) with reduced expression of the epithelial marker E-cadherin and elevated expression of multiple mesenchymal markers (FSP-1, α-SMA, and desmin). Interestingly, 19,20-EDP treatment reduced renal EMT in UUO by decreasing mesenchymal and increasing epithelial marker expression. Overall, we demonstrate that a novel omega-3 fatty acid metabolite 19,20-EDP, prevents UUO-induced renal fibrosis in mice by reducing renal EMT. PMID:27213332

  10. Epidemiology of Idiopathic Pulmonary Fibrosis in Northern Italy.

    Directory of Open Access Journals (Sweden)

    Sergio Harari

    Full Text Available Idiopathic pulmonary fibrosis (IPF is the most common and severe form of idiopathic interstitial pneumonia. Despite its clinical relevance, few studies have examined the epidemiology of IPF and temporal variation in disease incidence and prevalence. Aim of the study was to investigate the prevalence, incidence and trends of IPF in Lombardy, a region with nearly 10 million inhabitants, during 2005-2010.For the identification of IPF patients, we used healthcare administrative databases of Lombardy Healthcare System and adopted three algorithms: generic, broad and narrow case definition (GCD, BCD, NCD. IPF cases were identified according to diagnoses reported in inpatient and outpatient claims occurred during 2000-2010. We estimated age- and sex-adjusted annual prevalence and incidence rates from 2005 to 2010, thus allowing for a 5-year washout period.The mean annual incidence rate was estimated at 2.3 and 5.3 per 100,000 person-years using NCD and GCD, respectively. IPF incidence was higher among males, and increased with age. Trend remained stable over the years. The estimated annual prevalence rate was 35.5, 22.4, and 12.6 per 100,000 person-years using GCD, BCD and NCD, respectively, and increased with age. Moreover, we observed a positive trend over the years. Using BCD and NCD, prevalence was higher among males.The results of this study, which is one of the largest population-based survey ever conducted according to strict criteria, indicated that prevalence of IPF increased across the years while incidence remained stable, thus suggesting that survival with IPF has improved.

  11. Screening for Helicobacter pylori in Idiopathic Pulmonary Fibrosis Lung Biopsies.

    Science.gov (United States)

    Kreuter, Michael; Kirsten, Detlef; Bahmer, Thomas; Penzel, Roland; Claussen, Martin; Ehlers-Tenenbaum, Svenja; Muley, Thomas; Palmowski, Karin; Eichinger, Monika; Leider, Marta; Herth, Felix J F; Rabe, Klaus F; Bittmann, Iris; Warth, Arne

    2016-01-01

    Increasing evidence suggests a role of gastro-oesophageal reflux (GER) in idiopathic pulmonary fibrosis (IPF) pathogenesis. Recently, an association between serum Helicobacter pylori (HP) antibody positivity and more severe disease was described, but HP has not been directly analysed in lung tissue so far. To investigate the presence of HP in the lung tissue of IPF patients. Two tertiary interstitial lung disease care centre databases were screened for available lung biopsy material from IPF patients. Clinical and radiological data, including presence of GER and antiacid medication, were evaluated. HP-specific PCR was carried out on the IPF lung biopsy specimens. A total of 39 IPF patients were included, of whom 85% were male. The patients' median age was 66 years, their vital capacity was 79% predicted, and their diffusing capacity for carbon monoxide was 53% predicted. In all, 82% of the lung biopsies were surgical and 18% transbronchial. Comorbidities were GER disease in 23% (n = 9), sleep apnoea in 13% (n = 5) and hiatal hernia in 38% of the cases (n = 15). Proton pump inhibitors were prescribed at the time of biopsy in 21% of the cases (n = 9). After a median follow-up of 25 months (range 6-69), there were 1 death, 1 lung transplantation and 8 acute exacerbations without relevant differences between the GER and non-GER subgroups. HP DNA was not detected in any of the lung tissue samples. The fact that no HP DNA was detected in the lung tissues calls into question the proposed relevance of HP to the direct pathogenesis of IPF. © 2015 S. Karger AG, Basel.

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

    Science.gov (United States)

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

    2017-04-01

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

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

    International Nuclear Information System (INIS)

    Si Jianhong

    2007-01-01

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

  14. Therapy of experimental NASH and fibrosis with galectin inhibitors.

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    Peter G Traber

    Full Text Available Non-alcoholic steatohepatitis (NASH and resultant liver fibrosis is a major health problem without effective therapy. Some data suggest that galectin-3 null mice are resistant to the development of NASH with fibrosis. We examined the ability of two complex carbohydrate drugs that bind galectin-3, GM-CT-01 and GR-MD-02, to treat NASH with fibrosis in a murine model. GR-MD-02 treatment resulted in marked improvement in liver histology with significant reduction in NASH activity and collagen deposition. Treatments seemed also to improve both glomerulopathy and interstitial fibrosis observed in kidneys. The improvement in liver histology was evident when animals were treated early in disease or after establishment of liver fibrosis. In all measures, GM-CT-01 had an intermediate effect between vehicle and GR-MD-02. Galectin-3 protein expression was increased in NASH with highest expression in macrophages surrounding lipid laden hepatocytes, and reduced following treatment with GR-MD-02, while the number of macrophages was unchanged. Treatment with GR-MD-02 also reduced the expression of pathological indicators including iNOS, an important TH1 inflammatory mediator, CD36, a scavenger receptor for lipoproteins on macrophages, and α-smooth muscle actin, a marker for activated stellate cells which are the primary collagen producing cells in liver fibrosis. We conclude that treatment with these galectin-3 targeting drugs improved histopathological findings of NASH and markedly reduced fibrosis in a murine model of NASH. While the mechanisms require further investigation, the treatment effect is associated with a reduction of galectin-3 expressed by activated macrophages which was associated with regression of NASH, including hepatocellular fat accumulation, hepatocyte ballooning, intra-portal and intra-lobular inflammatory infiltrate, and deposition of collagen. Similar effects were found with GM-CT-01, but with approximately four-fold lower potency than

  15. The impact of slice-reduced computed tomography on histogram-based densitometry assessment of lung fibrosis in patients with systemic sclerosis.

    Science.gov (United States)

    Nguyen-Kim, Thi Dan Linh; Maurer, Britta; Suliman, Yossra A; Morsbach, Fabian; Distler, Oliver; Frauenfelder, Thomas

    2018-04-01

    To evaluate usability of slice-reduced sequential computed tomography (CT) compared to standard high-resolution CT (HRCT) in patients with systemic sclerosis (SSc) for qualitative and quantitative assessment of interstitial lung disease (ILD) with respect to (I) detection of lung parenchymal abnormalities, (II) qualitative and semiquantitative visual assessment, (III) quantification of ILD by histograms and (IV) accuracy for the 20%-cut off discrimination. From standard chest HRCT of 60 SSc patients sequential 9-slice-computed tomography (reduced HRCT) was retrospectively reconstructed. ILD was assessed by visual scoring and quantitative histogram parameters. Results from standard and reduced HRCT were compared using non-parametric tests and analysed by univariate linear regression analyses. With respect to the detection of parenchymal abnormalities, only the detection of intrapulmonary bronchiectasis was significantly lower in reduced HRCT compared to standard HRCT (P=0.039). No differences were found comparing visual scores for fibrosis severity and extension from standard and reduced HRCT (P=0.051-0.073). All scores correlated significantly (Phistogram parameters derived from both, standard and reduced HRCT. Significant higher values of kurtosis and skewness for reduced HRCT were found (both Phistogram parameters from reduced HRCT showed significant discrimination at cut-off 20% fibrosis (sensitivity 88% kurtosis and skewness; specificity 81% kurtosis and 86% skewness; cut-off kurtosis ≤26, cut-off skewness ≤4; both Phistogram parameters derived from the approach of reduced HRCT could discriminate at a threshold of 20% lung fibrosis with high sensitivity and specificity. Hence it might be used to detect early disease progression of lung fibrosis in context of monitoring and treatment of SSc patients.

  16. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter; Skov, Lone; Rossen, Kristian

    2006-01-01

    Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases...... of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75...... d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P

  17. Syndecans in heart fibrosis.

    Science.gov (United States)

    Lunde, Ida G; Herum, Kate M; Carlson, Cathrine C; Christensen, Geir

    2016-09-01

    Heart disease is a deadly syndrome affecting millions worldwide. It reflects an unmet clinical need, and the disease mechanisms are poorly understood. Cardiac fibrosis is central to heart disease. The four-membered family of transmembrane proteoglycans, syndecan-1 to -4, is believed to regulate fibrosis. We review the current literature concerning syndecans in cardiac fibrosis. Syndecan expression is up-regulated in response to pro-inflammatory stimuli in various forms of heart disease with fibrosis. Mice lacking syndecan-1 and -4 show reduced activation of pro-fibrotic signaling and increased cardiac rupture upon infarction indicating an important role for these molecules. Whereas the short cytoplasmic tail of syndecans regulates signaling, their extracellular part, substituted with heparan sulfate glycosaminoglycan chains, binds a plethora of extracellular matrix (ECM) molecules involved in fibrosis, e.g., collagens, growth factors, cytokines, and immune cell adhesion proteins. Full-length syndecans induce pro-fibrotic signaling, increasing the expression of collagens, myofibroblast differentiation factors, ECM enzymes, growth factors, and immune cell adhesion molecules, thereby also increasing cardiac stiffness and preventing cardiac rupture. Upon pro-inflammatory stimuli, syndecan ectodomains are enzymatically released from heart cells (syndecan shedding). Shed ectodomains affect the expression of ECM molecules, promoting ECM degradation and cardiac rupture upon myocardial infarction. Blood levels of shed syndecan-1 and -4 ectodomains are associated with hospitalization, mortality, and heart remodeling in patients with heart failure. Improved understanding of syndecans and their modifying enzymes in cardiac fibrosis might contribute to the development of compounds with therapeutic potential, and enzymatically shed syndecan ectodomains might constitute a future prognostic tool for heart diseases with fibrosis. Graphical Abstract Graphical abstract summarizing

  18. Endomyocardial fibrosis in infancy

    Directory of Open Access Journals (Sweden)

    Jatene Marcelo Biscegli

    2003-01-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  20. Genome sequencing of idiopathic pulmonary fibrosis in conjunction with a medical school human anatomy course.

    Science.gov (United States)

    Kumar, Akash; Dougherty, Max; Findlay, Gregory M; Geisheker, Madeleine; Klein, Jason; Lazar, John; Machkovech, Heather; Resnick, Jesse; Resnick, Rebecca; Salter, Alexander I; Talebi-Liasi, Faezeh; Arakawa, Christopher; Baudin, Jacob; Bogaard, Andrew; Salesky, Rebecca; Zhou, Qian; Smith, Kelly; Clark, John I; Shendure, Jay; Horwitz, Marshall S

    2014-01-01

    Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF). Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP), as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a single nucleotide polymorphism (SNP), rs35705950, located in the promoter region of the gene encoding mucin glycoprotein MUC5B. The MUC5B promoter polymorphism was recently found to markedly elevate risk for IPF, though a particular association with NSIP has not been previously reported, nor has its contribution to disease risk previously been evaluated in the genome-wide context of all genetic variants. We did not identify additional predicted functional variants in a region of linkage disequilibrium (LD) adjacent to MUC5B, nor did we discover other likely risk-contributing variants elsewhere in the genome. Whole genome sequencing thus corroborates the association of rs35705950 with MUC5B dysregulation and interstitial lung disease. This novel exercise additionally served a unique mission in bridging clinical and basic science education.

  1. Genome sequencing of idiopathic pulmonary fibrosis in conjunction with a medical school human anatomy course.

    Directory of Open Access Journals (Sweden)

    Akash Kumar

    Full Text Available Even in cases where there is no obvious family history of disease, genome sequencing may contribute to clinical diagnosis and management. Clinical application of the genome has not yet become routine, however, in part because physicians are still learning how best to utilize such information. As an educational research exercise performed in conjunction with our medical school human anatomy course, we explored the potential utility of determining the whole genome sequence of a patient who had died following a clinical diagnosis of idiopathic pulmonary fibrosis (IPF. Medical students performed dissection and whole genome sequencing of the cadaver. Gross and microscopic findings were more consistent with the fibrosing variant of nonspecific interstitial pneumonia (NSIP, as opposed to IPF per se. Variants in genes causing Mendelian disorders predisposing to IPF were not detected. However, whole genome sequencing identified several common variants associated with IPF, including a single nucleotide polymorphism (SNP, rs35705950, located in the promoter region of the gene encoding mucin glycoprotein MUC5B. The MUC5B promoter polymorphism was recently found to markedly elevate risk for IPF, though a particular association with NSIP has not been previously reported, nor has its contribution to disease risk previously been evaluated in the genome-wide context of all genetic variants. We did not identify additional predicted functional variants in a region of linkage disequilibrium (LD adjacent to MUC5B, nor did we discover other likely risk-contributing variants elsewhere in the genome. Whole genome sequencing thus corroborates the association of rs35705950 with MUC5B dysregulation and interstitial lung disease. This novel exercise additionally served a unique mission in bridging clinical and basic science education.

  2. Myodegeneration with fibrosis and regeneration in the pectoralis major muscle of broilers.

    Science.gov (United States)

    Sihvo, H-K; Immonen, K; Puolanne, E

    2014-05-01

    A myopathy affecting the pectoralis major muscle of the commercial broiler has emerged creating remarkable economic losses as well as a potential welfare problem of the birds. We here describe the macroscopic and histologic lesions of this myopathy within 10 pectoralis major muscles of 5- to 6-week-old broilers in Finland. Following macroscopic evaluation and palpation of the muscles, a tissue sample of each was fixed in formalin, processed for histology, and histologically evaluated. The muscles that were macroscopically hard, outbulging, pale, and often accompanied with white striping histologically exhibited moderate to severe polyphasic myodegeneration with regeneration as well as a variable amount of interstitial connective tissue accumulation or fibrosis. All affected cases also exhibited perivenular lymphocyte accumulation. The etiology of this myodegenerative lesion remains yet open. Polyphasic myodegeneration is associated with several previously known etiologies, but palpatory hardness focusing on the pectoralis major, together with perivenular lymphocytes, has not been described in relation to them. The results of this study provide the pathological basis for further studies concerning the etiology of the currently described myopathy.

  3. [Modern Views on Children's Interstitial Lung Disease].

    Science.gov (United States)

    Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

    2015-01-01

    Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.

  4. Radiation enhances silica translocation to the pulmonary interstitium and increases fibrosis in mice

    International Nuclear Information System (INIS)

    Adamson, I.Y.R.

    1992-01-01

    The effects of whole body irradiation (WBR) on particle clearance and the development of pulmonary fibrosis have been investigated. Using carbon, clearance is accomplished by polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM), and only a few particles reach the interstitum. However, in preirradiated mice, the usual eflux of inflammatory cells is much delayed so that more free carbon remains in the alveoli, and by 1 week, many particles cross the epithelium to be phagocytized by interstitial macrophages. Carbon is found in the peribronchiolar interstitium 6 months later with no evidence of fibrosis. In the present study, mice received 1 mg silica intratracheally 2 days after 6.5 Gy WBR when the white blood cell count was low. A much-reduced Am and PMN response was found in the following 2 weeks compared to the reaction to silica alone, and many silica particles reached interstitial macrophages. In this case, macrophage activation by silica was associated with fibroblast proliferation, and by 16 weeks, much more pulmonary fibrosis was produced than after silica or irradiation only. This was measured biochemically and correlated with a large increase in retained silica in the irradiation-silica group. The results indicate that radiation inhibits the inflammatory response to particle instillation, resulting in greater translocation of free particles to the pulmonary interstitium. In the case of silica, the greater, prolonged interaction with interstitial macrophages leads to a much exaggerated fibrotic reaction. 17 refs., 11 figs

  5. Idiopathic pulmonary fibrosis misdiagnosed as sputum-negative pulmonary tuberculosis.

    Science.gov (United States)

    Isah, Muhammad Danasabe; Abbas, Aminu; Abba, Abdullahi A; Umar, Mohammed

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is one of a spectrum of idiopathic interstitial pneumonia. IPF is an increasingly common condition which poses many diagnostic and therapeutic challenges leading to misdiagnosis and mismanagement. We presented a 55-year-old male textile trader who was initially managed as sputum-negative pulmonary tuberculosis before histology report. He presented to our clinic with Breathlessness and cough of 3 years and 2.5 years, respectively. He had commenced anti-tuberculosis two months before presentation without significant relief. General Physical examination and vital signs were essentially normal. SPO2 was 96% on room air. Chest Examination revealed end-inspiratory bi-basal velcro-like crackles. Other systemic examinations were normal. Radiological examination by way of chest X- ray and chest CT showed features suggestive of IPF. The patient also had open Lung biopsy for histology and spirometry which demonstrated restrictive ventilatory function pattern. A diagnosis of Interstitial lung disease probably Idiopathic Pulmonary Fibrosis was entertained. He was commenced on Tab prednisolone, Tab Rabeprazole, with minimal improvement. IPF have often been misdiagnosed and treated as pulmonary tuberculosis with unfavorable outcome.

  6. Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jamille Souza Fernandes

    2014-01-01

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

  7. Di-interstitial defect in silicon revisited

    International Nuclear Information System (INIS)

    Londos, C. A.; Antonaras, G.; Chroneos, A.

    2013-01-01

    Infrared spectroscopy was used to study the defect spectrum of Cz-Si samples following fast neutron irradiation. We mainly focus on the band at 533 cm −1 , which disappears from the spectra at ∼170 °C, exhibiting similar thermal stability with the Si-P6 electron paramagnetic resonance (EPR) spectrum previously correlated with the di-interstitial defect. The suggested structural model of this defect comprises of two self-interstitial atoms located symmetrically around a lattice site Si atom. The band anneals out following a first-order kinetics with an activation energy of 0.88 ± 0.3 eV. This value does not deviate considerably from previously quoted experimental and theoretical values for the di-interstitial defect. The present results indicate that the 533 cm −1 IR band originates from the same structure as that of the Si-P6 EPR spectrum

  8. An overview of interstitial brachytherapy and hyperthermia

    International Nuclear Information System (INIS)

    Brandt, B.B.; Harney, J.

    1989-01-01

    Interstitial thermoradiotherapy, an experimental cancer treatment that combines interstitial radiation implants (brachytherapy) and interstitial hyperthermia, is in the early stages of investigation. In accordance with the procedure used in a current national trial protocol, a 60-minute hyperthermia treatment is administered after catheters are placed into the tumor area while the patient is under general anesthesia. This is immediately followed by loading of radioactive Iridium-192 seeds into the catheters for a defined period of time. Once the prescribed radiation dose is delivered, the radioactive sources are removed and a second, 60-minute hyperthermia treatment is administered. Clinical trials with hyperthermia in combination with radiation have increased in recent years. Nurses caring for these patients need to become more knowledgeable about this investigational therapy. This paper provides an overview of the biologic rationale for this therapy, as well as a description of the delivery method and clinical application. Specific related nursing interventions are defined in a nursing protocol.23 references

  9. Idiopathic interstitial pneumonias: radiologic-pathologic correlation

    International Nuclear Information System (INIS)

    Yoon, Young Cheol; Suh, Gee Young; Han, Joung Ho; Lee, Kyung Soo

    2002-01-01

    Idiopathic interstitial pneumonias are at present classified as one of four types: usual, nonspecific, acute, or desquamative. The acute form has the worst prognosis, followed by the usual and the nonspecific form; it is in desquamative cases that prognosis is best. At high-resolution CT, usual interstitial pneumonia, the most frequent type, manifests as patchy subpleural areas of ground-glass attenuation, irregular linear opacity, and honeycombing, which the nonspecific type, the second most frequent, appears as subpleural patchy areas of ground-glass attenuation with associated areas of irregular linear opacity. Acute interstitial pneumonia demonstrates extensive bilateral airspace consolidation and patchy or diffuse bilateral areas of ground-glass attenuation in middle and lower lung zones

  10. Cystic fibrosis in adults

    Directory of Open Access Journals (Sweden)

    C. Damas

    2007-05-01

    Full Text Available 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 ΔF508 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 Resumo: Os autores efectuaram uma revisão de doentes adultos com fibrose quística (FQ, seguidos na consulta de Pneumologia no período de 1994-2004 (n = 8: cinco mulheres e três homens, com idades compreendidas entre 20 e 34 anos (mediana  =  27 anos, cuja idade de diagnóstico variou entre os 18 meses e os 31 anos.O diagnóstico foi obtido por prova de suor (positiva em seis doentes e estudo genético (homozigotia para a mutação ΔF508 em

  11. Idiopathic interstitial pneumonias: imaging-pathology correlation

    International Nuclear Information System (INIS)

    Ellis, Stephen M.; Hansell, David M.

    2002-01-01

    The terminology related to idiopathic interstitial pneumonia (IIP) remains confusing and in some cases wholly inaccurate. In addition, a greater understanding of the correlation between high-resolution computed tomography (HRCT) appearances and the corresponding histopathological changes found in the interstitial pneumonias has resulted in a crucial role for HRCT in the investigation of IIPs. The role of the radiologist is becoming increasingly important with a strong emphasis on establishing a diagnosis without resorting to lung biopsy. We aim to clarify the current classification of the IIPs highlighting their clinical, pathological and imaging characteristics in order to assist the radiologist in performing their increasingly important diagnostic role. (orig.)

  12. Quantum diffusion of light interstitials in metals

    International Nuclear Information System (INIS)

    McMullen, T.; Bergersen, B.

    1978-01-01

    A quantum theory of diffusion of self-trapped light interstitials in metals is presented. The theory encompasses both coherent and incoherent tunneling, but the approximation used neglects the dependence of the interstitial transfer matrix element on the vibrational state of the crystal. The coherent tunneling contribution is estimated by fitting the incoherent diffusion rate to experimental data for hydrogen and muon diffusion. It is predicted that coherent diffusion should be dominant below approximately 80 K for H in Nb and below approximately 190 K for μ + in Cu. Experimental verifications of these predictions would require high purity strain free samples and low concentrations of the diffusing species. (author)

  13. Co-morbidities of Interstitial Cystitis

    Directory of Open Access Journals (Sweden)

    Gisela eChelimsky

    2012-08-01

    Full Text Available Introduction: This study aimed to estimate the proportion of patients with Interstitial Cystitis/Painful Bladder Syndrome (IC/BPS with systemic dysfunction associated co-morbidities such as irritable bowel syndrome (IBS and fibromyalgia (FM. Material and Methods: Two groups of subjects with IC/BPS were included: 1 Physician diagnosed patients with IC/BPS and 2 Subjects meeting NIDDK IC/PBS criteria based on a questionnaire (ODYSA. These groups were compared to healthy controls matched for age and socio-economic status. NIDDK criteria required: pain with bladder filling that improves with emptying, urinary urgency due to discomfort or pain, polyuria > 11 times/24 hrs, and nocturia > 2 times/night. The ODYSA instrument evaluates symptoms pertaining to a range of disorders including chronic fatigue, orthostatic intolerance, syncope, IBS, dyspepsia, cyclic vomiting syndrome, headaches and migraines, sleep, Raynaud’s syndrome and chronic aches and pains. Results: IC/BPS was diagnosed in 26 subjects (mean age 47 +/- 16 yrs, 92% females, 58 had symptoms of IC/BPS by NIDDK criteria, (mean age 40 +/- 17 yrs, 79% females and 48 were healthy controls (mean age 31+/- 14 yrs, mean age 77%. Co-morbid complaints in the IC/BPS groups included gastrointestinal symptoms suggestive of IBS and dyspepsia, sleep abnormalities with delayed onset of sleep, feeling poorly refreshed in the morning, waking up before needed, snoring, severe chronic fatigue and chronic generalized pain, migraines and syncope. Discussion: Patients with IC/BPS had co-morbid central and autonomic nervous system disorders. Our findings mirror those of others in regard to IBS, symptoms suggestive of FM, chronic pain and migraine. High rates of syncope and functional dyspepsia found in the IC/BPS groups merit further study to determine if IC/BPS is part of a diffuse disorder of central, autonomic and sensory processing affecting multiple organs outside the bladder.

  14. Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5.

    Directory of Open Access Journals (Sweden)

    Kurt J Williams

    Full Text Available Gammaherpesviruses (γHV are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF, a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg was significantly increased compared to control horses (26 µg/mg (p < 0.5, as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4% (mean ± SEM; p < 0.001. Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host.

  15. Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5.

    Science.gov (United States)

    Williams, Kurt J; Robinson, N Edward; Lim, Ailam; Brandenberger, Christina; Maes, Roger; Behan, Ashley; Bolin, Steven R

    2013-01-01

    Gammaherpesviruses (γHV) are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg) was significantly increased compared to control horses (26 µg/mg) (p < 0.5), as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4%) (mean ± SEM; p < 0.001). Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host.

  16. Biopsy in idiopathic pulmonary fibrosis: back to the future.

    Science.gov (United States)

    Rossi, Giulio; Spagnolo, Paolo

    2017-09-01

    Idiopathic Pulmonary Fibrosis (IPF) is a relentlessly progressive, fibrosing interstitial pneumonia characterized by a radiologic and/or histologic pattern of usual interstitial pneumonia (UIP). The availability of two effective anti-fibrotic drugs in IPF has encouraged the identification and treatment of patients in early stages in order to maximize clinical benefit. The ability of high-resolution computed tomography (HRCT) to identify a 'definite' UIP pattern is suboptimal, particularly in the absence of honeycombing. Therefore, radiologic criteria for UIP are currently being redefined. Histology represents the major source of information to define a UIP pattern. Novel and less invasive approaches (particularly cryobiopsy) to sample interstitial lung diseases have demonstrated high sensitivity and specificity. In parallel, researchers are focusing on molecular mechanisms underlying IPF with the aim to identify more specific druggable targets. Lung tissue is therefore essential for diagnostic, pathogenetic and therapeutic purposes. Areas covered: We identified and critically reviewed the most relevant recent literature related to the limitations of current radiologic criteria, new lung sampling procedures, and molecular pathways in support of the need of lung tissue to better understand IPF. Expert commentary: The development of truly effective treatments for IPF requires the identification of key pathogenetic molecules and pathways. To this end, the availability of lung tissue is vital.

  17. Grape seed extract ameliorates bleomycin-induced mouse pulmonary fibrosis.

    Science.gov (United States)

    Liu, Qi; Jiang, Jun-Xia; Liu, Ya-Nan; Ge, Ling-Tian; Guan, Yan; Zhao, Wei; Jia, Yong-Liang; Dong, Xin-Wei; Sun, Yun; Xie, Qiang-Min

    2017-05-05

    Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity. Although it has been found that GSE can improve the lung collagen deposition and fibrosis pathology induced by bleomycin in rat, its effects on pulmonary function, inflammation, growth factors, matrix metalloproteinases and epithelial-mesenchymal transition remain to be researched. In the present study, we studied whether GSE provided protection against bleomycin (BLM)-induced mouse pulmonary fibrosis. ICR strain mice were treated with BLM in order to establish pulmonary fibrosis models. GSE was given daily via intragastric administration for three weeks starting at one day after intratracheal instillation. GSE at 50 or 100mg/kg significantly reduced BLM-induced inflammatory cells infiltration, proinflammatory factor protein expression, and hydroxyproline in lung tissues, and improved pulmonary function in mice. Additionally, treatment with GSE also significantly impaired BLM-induced increases in lung fibrotic marker expression (collagen type I alpha 1 and fibronectin 1) and decreases in an anti-fibrotic marker (E-cadherin). Further investigation indicated that the possible molecular targets of GSE are matrix metalloproteinases-9 (MMP-9) and TGF-β1, given that treatment with GSE significantly prevented BLM-induced increases in MMP-9 and TGF-β1 expression in the lungs. Together, these results suggest that supplementation with GSE may improve the quality of life of lung fibrosis patients by inhibiting MMP-9 and TGF-β1 expression in the lungs. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The COPD Assessment Test as a Prognostic Marker in Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Fujiko Someya

    2016-01-01

    Full Text Available The chronic obstructive pulmonary disease (COPD Assessment Test (CAT, which was developed to measure the health status of patients with COPD, was applied to patients with interstitial lung disease, aiming to examine the CAT as a predictor of outcome. Over a follow-up period of more than one year, 101 consecutive patients with interstitial lung disease were evaluated by the CAT. The CAT scores of 40 in total were categorized into four subsets according to the severity. Patients with higher (more severe scores exhibited lower forced vital capacity and lung diffusion capacity for carbon monoxide. The survival rate was significantly lower in patients with higher scores (log-rank test, P = 0.0002, and the hazard ratios for death of the higher scores and lower lung diffusion capacity for carbon monoxide were independently significant. These findings suggest that CAT can indicate the risk of mortality in patients with interstitial lung disease.

  19. Successful Immunoglobulin Treatment in Severe Cryptogenic Organizing Pneumonia Caused by Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Dong Hoon Lee

    2015-08-01

    Full Text Available In connective tissue diseases, autoantibodies cause pulmonary interstitial inflammation and fibrosis, and patients require treatment with an immunosuppressive agent such as a steroid. Dermatomyositis is an incurable, uncommon form of connective tissue disease that occasionally causes diffuse pulmonary inflammation leading to acute severe respiratory failure. In such cases, the prognosis is very poor despite treatment with high-dose steroid. In the present case, a 46-year-old man was admitted to our hospital with dyspnea. He was diagnosed with dermatomyositis combined with cryptogenic organizing pneumonia (COP with respiratory failure and underwent treatment with steroid and an immunosuppressive agent, but the COP was not improved. However, the respiratory failure did improve after treatment with intravenous immunoglobulin, which therefore can be considered a treatment option in cases where steroids and immunosuppressive agents are ineffective.

  20. 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.

  1. Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Luciana Santos Cardoso

    2013-01-01

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

  2. Contribution of denervated muscle to contractures after neonatal brachial plexus injury: not just muscle fibrosis.

    Science.gov (United States)

    Nikolaou, Sia; Liangjun, Hu; Tuttle, Lori J; Weekley, Holly; Christopher, Wylie; Lieber, Richard L; Cornwall, Roger

    2014-03-01

    We investigated the contribution of muscle fibrosis to elbow flexion contractures in a murine model of neonatal brachial plexus injury (NBPI). Four weeks after NBPI, biceps and brachialis fibrosis were assessed histologically and compared with the timing of contracture development and the relative contribution of each muscle to contractures. Modulus of elasticity and hydroxyproline (collagen) content were measured and correlated with contracture severity. The effect of halofuginone antifibrotic therapy on fibrosis and contractures was investigated. Elbow contractures preceded muscle fibrosis development. The brachialis was less fibrotic than the biceps, yet contributed more to contractures. Modulus and hydroxyproline content increased in both elbow flexors, but neither correlated with contracture severity. Halofuginone reduced biceps fibrosis but did not reduce contracture severity. Contractures after NBPI cannot be explained solely by muscle fibrosis, arguing for investigation of alternate pathophysiologic targets for contracture prevention and treatment. Copyright © 2013 Wiley Periodicals, Inc.

  3. Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

    DEFF Research Database (Denmark)

    Kellenberger, Terese; Marcussen, Niels; Nyengaard, Jens Randel

    2014-01-01

    Late renal graft loss is associated with interstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) is thought to facilitate fibrosis through interaction with TGF-β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate...... transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival...... was not significantly correlated to HIF-1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1-10-72-318-13)....

  4. Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

    Science.gov (United States)

    Kim, J K; Yuen, D A; Leung, G; Jothy, S; Zaltzman, J; Ramesh Prasad, G V; Prabhudesai, V; Mnatzakanian, G; Kirpalani, A

    2017-09-01

    A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Serum metabonomic analysis of protective effects of Curcuma aromatica oil on renal fibrosis rats.

    Science.gov (United States)

    Zhao, Liangcai; Zhang, Haiyan; Yang, Yunjun; Zheng, Yongquan; Dong, Minjian; Wang, Yaqiang; Bai, Guanghui; Ye, Xinjian; Yan, Zhihan; Gao, Hongchang

    2014-01-01

    Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on. Nuclear magnetic resonance (NMR)-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data. The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

  6. Endostatin and transglutaminase 2 are involved in fibrosis of the aging kidney.

    Science.gov (United States)

    Lin, Chi Hua Sarah; Chen, Jun; Zhang, Zhongtao; Johnson, Gail V W; Cooper, Arthur J L; Feola, Julianne; Bank, Alexander; Shein, Jonathan; Ruotsalainen, Heli J; Pihlajaniemi, Taina A; Goligorsky, Michael S

    2016-06-01

    Endostatin (EST), an antiangiogenic factor, is enriched in aging kidneys. EST is also an interactive partner of transglutaminase 2 (TG2), an enzyme that cross-links extracellular matrix proteins. Here we tested whether EST and TG2 play a role in the fibrosis of aging. In wild-type mice, aging kidneys exhibited a 2- to 4-fold increase in TG2 paralleled by increased cross-linked extracellular matrix proteins and fibrosis. Mice transgenic to express EST showed renal fibrosis at a young age. One-month delivery of EST via minipumps to young mice showed increased renal fibrosis that became more robust when superimposed on folic acid-induced nephropathy. Upregulated TG2 and impaired renal function were apparent with EST delivery combined with folic acid-induced nephropathy. Subcapsular injection of TG2 and/or EST into kidneys of young mice not only induced interstitial fibrosis, but also increased the proportion of senescent cells. Thus, kidney fibrosis in aging may represent a natural outcome of upregulated EST and TG2, but more likely it appears to be a result of cumulative stresses occurring on the background of synergistically acting geronic (aging) proteins, EST and TG2. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  7. Endostatin and transglutaminase 2 are involved in fibrosis of the aging kidney

    Science.gov (United States)

    Lin, Chi Hua Sarah; Chen, Jun; Zhang, Zhongtao; Johnson, Gail; Cooper, Arthur JL; Feola, Julianne; Bank, Alexander; Shein, Jonathan; Ruotsalainen, Heli; Pihlajaniemi, Taina; Goligorsky, Michael S

    2016-01-01

    Endostatin (EST), an anti-angiogenic factor, is enriched in aging kidneys. EST is also an interactive partner of transglutaminase 2 (TG2), an enzyme that cross-links extracellular matrix proteins. Here we tested whether EST and TG2 play a role in the fibrosis of aging. In wild type mice, aging kidneys exhibited a 2–4 fold increase in TG2 paralleled by increased cross-linked extracellular matrix proteins and fibrosis. Mice transgenic to express EST showed renal fibrosis at a young age. One month delivery of EST via minipumps to young mice showed increased renal fibrosis that became more robust when superimposed on folic acid-induced nephropathy. Upregulated TG2 and impaired renal function were apparent with EST delivery combined with folic acid-induced nephropathy. Subcapsular injection of TG2 and/or EST into kidneys of young mice not only induced interstitial fibrosis, but also increased the proportion of senescent cells. Thus, kidney fibrosis in aging may represent a natural outcome of upregulated EST and TG2, but more likely it appears to be a result of cumulative stresses occurring on the background of synergistically acting geronic (aging) proteins, EST and TG2. PMID:27165830

  8. A mouse model for inherited renal fibrosis associated with endoplasmic reticulum stress

    Directory of Open Access Journals (Sweden)

    Sian E. Piret

    2017-06-01

    Full Text Available Renal fibrosis is a common feature of renal failure resulting from multiple etiologies, including diabetic nephropathy, hypertension and inherited renal disorders. However, the mechanisms of renal fibrosis are incompletely understood and we therefore explored these by establishing a mouse model for a renal tubular disorder, referred to as autosomal dominant tubulointerstitial kidney disease (ADTKD due to missense uromodulin (UMOD mutations (ADTKD-UMOD. ADTKD-UMOD, which is associated with retention of mutant uromodulin in the endoplasmic reticulum (ER of renal thick ascending limb cells, is characterized by hyperuricemia, interstitial fibrosis, inflammation and renal failure, and we used targeted homologous recombination to generate a knock-in mouse model with an ADTKD-causing missense cysteine to arginine uromodulin mutation (C125R. Heterozygous and homozygous mutant mice developed reduced uric acid excretion, renal fibrosis, immune cell infiltration and progressive renal failure, with decreased maturation and excretion of uromodulin, due to its retention in the ER. The ER stress marker 78 kDa glucose-regulated protein (GRP78 was elevated in cells expressing mutant uromodulin in heterozygous and homozygous mutant mice, and this was accompanied, both in vivo and ex vivo, by upregulation of two unfolded protein response pathways in primary thick ascending limb cells from homozygous mutant mice. However, this did not lead to an increase in apoptosis in vivo. Thus, we have developed a novel mouse model for renal fibrosis, which will be a valuable resource to decipher the mechanisms linking uromodulin mutations with ER stress and renal fibrosis.

  9. Cordyceps sinensis attenuates renal fibrosis and suppresses BAG3 induction in obstructed rat kidney.

    Science.gov (United States)

    Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Zong, Zhi-Hong; Du, Zhen-Xian; Li, De-Tian; Wang, Hua-Qin; Liu, Bo; Miao, Jia-Ning; Bian, Xiao-Hui

    2015-01-01

    BAG3 regulates a number of cellular processes, including cell proliferation, apoptosis, adhesion and migration, and epithelial-mesenchymal transition (EMT). However, the role of BAG3 in renal tubular EMT and renal interstitial fibrosis remains elusive. This study aimed to examine the dynamic expression of BAG3 during renal fibrosis, and to investigate the efficacy of Cordyceps sinensis (C. sinensis) on renal fibrosis. A rat model of unilateral ureteral obstruction (UUO) was established, and the expression of BAG3 and α-SMA, and the efficacy of C. sinensis on renal fibrosis induced by UUO were examined. The results showed that UUO led to collagen accumulation, which was significantly suppressed by C. sinensis. UUO increased the expression of BAG3 and α-SMA, a mesenchymal marker, while UUO induced BAG3 and α-SMA expression was significantly inhibited by C. sinensis. In addition, immunohistochemical staining demonstrated that BAG3 immunoreactivity was restricted to tubular epithelium. In conclusion, BAG3 is a potential target for the prevention and/or treatment of renal fibrosis, and C. Sinensis is a promising agent for renal fibrosis.

  10. MicroRNA mimicry blocks pulmonary fibrosis

    Science.gov (United States)

    Montgomery, Rusty L; Yu, Guoying; Latimer, Paul A; Stack, Christianna; Robinson, Kathryn; Dalby, Christina M; Kaminski, Naftali; van Rooij, Eva

    2014-01-01

    Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular disease. While many studies have shown therapeutic efficacy using miRNA inhibitors, efforts to restore or increase the function of a miRNA have been lagging behind. The miR-29 family has gained a lot of attention for its clear function in tissue fibrosis. This fibroblast-enriched miRNA family is downregulated in fibrotic diseases which induces a coordinate increase of many extracellular matrix genes. Here, we show that intravenous injection of synthetic RNA duplexes can increase miR-29 levels in vivo for several days. Moreover, therapeutic delivery of these miR-29 mimics during bleomycin-induced pulmonary fibrosis restores endogenous miR-29 function whereby decreasing collagen expression and blocking and reversing pulmonary fibrosis. Our data support the feasibility of using miRNA mimics to therapeutically increase miRNAs and indicate miR-29 to be a potent therapeutic miRNA for treating pulmonary fibrosis. PMID:25239947

  11. Pancreatic changes in cystic fibrosis: CT and sonographic appearances

    International Nuclear Information System (INIS)

    Daneman, A.; Gaskin, K.; Martin, D.J.; Cutz, E.

    1983-01-01

    The computed tomographic (CT) and sonographic appearances of the late stages of pancreatic damage in three patients with cystic fibrosis are illustrated. All three had severe exocrine pancreatic insufficiency with steatorrhea. In two patients CT revealed complete fatty replacement of the entire pancreas. In the third, increased echogenicity of the pancreas on sonography and the inhomogeneous attenuation on CT were interpreted as being the result of a combination of fibrosis, fatty replacement, calcification, and probable cyst formation

  12. Interstitial laser thermotherapy in neurosurgery: a review

    NARCIS (Netherlands)

    Menovsky, T.; Beek, J. F.; van Gemert, M. J.; Roux, F. X.; Bown, S. G.

    1996-01-01

    One of the most recent laser treatment modalities in neurosurgery is interstitial laser thermotherapy (ILTT). In this review, experimental and clinical studies concerning intracranial ILTT are discussed. Two methods for intra-operative control of the laser induced lesions are described; i.e.,

  13. Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

    Science.gov (United States)

    Mukhopadhyay, Sanjay; Parambil, Joseph G

    2012-10-01

    Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. A Case of Yellow Nail Syndrome Accompanying Idiopathic Interstitial Pneumonia; Successful Treatment with Clarithromycin, Methylprednisolone, and Alpha-Tocopherol

    Directory of Open Access Journals (Sweden)

    Bilge Yılmaz Kara

    2017-12-01

    Full Text Available A 51-year-old woman presented with complaints of dyspnea, fatigue, and non-productive cough. Chest X-ray showed bilateral lung infiltrates. Nonspecific air-space consolidation on anterior segment of the right lower lobe, bilateral bronchiectasis and infiltrates, patchy ground-glass opacities, and interstitial thickening were reported on thorax computed tomography which was non-responsive to antibiotics. After tru-cut biopsy which only revealed a single granuloma in a particular area, alveolar septal thickening and fibrosis, slight chronic inflammation with findings of congestion, lung involvement was considered to be associated with nonspecific interstitial pneumonia. The nails on all fingers displayed yellow discoloration with mild edema in the face and the legs. The final diagnosis was yellow nail syndrome. Short-term clarithromycin and long-term oral methylprednisolone with vitamin E treatment were successful. After 4 months, all components of the syndrome almost completely regressed.

  15. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

    Science.gov (United States)

    Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

    2008-01-01

    Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

  16. Recent advances in understanding idiopathic pulmonary fibrosis

    Science.gov (United States)

    Daccord, Cécile; Maher, Toby M.

    2016-01-01

    Despite major research efforts leading to the recent approval of pirfenidone and nintedanib, the dismal prognosis of idiopathic pulmonary fibrosis (IPF) remains unchanged. The elaboration of international diagnostic criteria and disease stratification models based on clinical, physiological, radiological, and histopathological features has improved the accuracy of IPF diagnosis and prediction of mortality risk. Nevertheless, given the marked heterogeneity in clinical phenotype and the considerable overlap of IPF with other fibrotic interstitial lung diseases (ILDs), about 10% of cases of pulmonary fibrosis remain unclassifiable. Moreover, currently available tools fail to detect early IPF, predict the highly variable course of the disease, and assess response to antifibrotic drugs. Recent advances in understanding the multiple interrelated pathogenic pathways underlying IPF have identified various molecular phenotypes resulting from complex interactions among genetic, epigenetic, transcriptional, post-transcriptional, metabolic, and environmental factors. These different disease endotypes appear to confer variable susceptibility to the condition, differing risks of rapid progression, and, possibly, altered responses to therapy. The development and validation of diagnostic and prognostic biomarkers are necessary to enable a more precise and earlier diagnosis of IPF and to improve prediction of future disease behaviour. The availability of approved antifibrotic therapies together with potential new drugs currently under evaluation also highlights the need for biomarkers able to predict and assess treatment responsiveness, thereby allowing individualised treatment based on risk of progression and drug response. This approach of disease stratification and personalised medicine is already used in the routine management of many cancers and provides a potential road map for guiding clinical care in IPF. PMID:27303645

  17. Predictors of the clinical effects of pirfenidone on idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Arai, Toru; Inoue, Yoshikazu; Sasaki, Yumiko; Tachibana, Kazunobu; Nakao, Keiko; Sugimoto, Chikatoshi; Okuma, Tomohisa; Akira, Masanori; Kitaichi, Masanori; Hayashi, Seiji

    2014-03-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. Recently, pirfenidone was reported to slow the rate of decline in vital capacity and improve progression-free survival in IPF. The purpose of this study was to clarify the factors that predicted a good response to pirfenidone, as well as its adverse effects. Forty-one IPF cases, treated with pirfenidone from January 2009 to January 2011, were enrolled in this investigation. Disease severity was classified into grades I-IV, as defined by the Japanese Respiratory Society (JRS). Short-term responsiveness to pirfenidone was evaluated by the modified criteria of the JRS. Predictors of nausea, anorexia, or both that represented important adverse effects were examined by multivariate Cox proportional hazard analyses. Predictors of short-time responsiveness were examined by multivariate logistic regression analyses. Diagnosed by a surgical lung biopsy (SLB), the mild cases of grade I/II were predictors of good, short-term responsiveness. Patients taking acid-secretion inhibitors, including proton pump inhibitors and histamine H2-receptor antagonists, showed less anorexia, nausea, or both. Only 1 case was administered drugs to activate gastrointestinal motility. We concluded that IPF patients with a mild disease, diagnosis by SLB, or both showed indications of a good response to pirfenidone. In addition, acid-secretion inhibitors may reduce the frequency of anorexia, nausea, or both from pirfenidone. © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  18. Time course of polyhexamethyleneguanidine phosphate-induced lung inflammation and fibrosis in mice.

    Science.gov (United States)

    Song, Jeongah; Kim, Woojin; Kim, Yong-Bum; Kim, Bumseok; Lee, Kyuhong

    2018-04-15

    Pulmonary fibrosis is a chronic progressive disease with unknown etiology and has poor prognosis. Polyhexamethyleneguanidine phosphate (PHMG-P) causes acute interstitial pneumonia and pulmonary fibrosis in humans when it exposed to the lung. In a previous study, when rats were exposed to PHMG-P through inhalation for 3 weeks, lung inflammation and fibrosis was observed even after 3 weeks of recovery. In this study, we aimed to determine the time course of PHMG-P-induced lung inflammation and fibrosis. We compared pathological action of PHMG-P with that of bleomycin (BLM) and investigated the mechanism underlying PHMG-P-induced lung inflammation and fibrosis. PHMG-P (0.9 mg/kg) or BLM (1.5 mg/kg) was intratracheally administered to mice. At weeks 1, 2, 4 and 10 after instillation, the levels of inflammatory and fibrotic markers and the expression of inflammasome proteins were measured. The inflammatory and fibrotic responses were upregulated until 10 and 4 weeks in the PHMG-P and BLM groups, respectively. Immune cell infiltration and considerable collagen deposition in the peribronchiolar and interstitial areas of the lungs, fibroblast proliferation, and hyperplasia of type II epithelial cells were observed. NALP3 inflammasome activation was detected in the PHMG-P group until 4 weeks, which is suspected to be the main reason for the persistent inflammatory response and exacerbation of fibrotic changes. Most importantly, the pathological changes in the PHMG-P group were similar to those observed in humidifier disinfectant-associated patients. A single exposure of PHMG-P led to persistent pulmonary inflammation and fibrosis for at least 10 weeks. Copyright © 2018. Published by Elsevier Inc.

  19. An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis.

    Science.gov (United States)

    Petrovski, Slavé; Todd, Jamie L; Durheim, Michael T; Wang, Quanli; Chien, Jason W; Kelly, Fran L; Frankel, Courtney; Mebane, Caroline M; Ren, Zhong; Bridgers, Joshua; Urban, Thomas J; Malone, Colin D; Finlen Copeland, Ashley; Brinkley, Christie; Allen, Andrew S; O'Riordan, Thomas; McHutchison, John G; Palmer, Scott M; Goldstein, David B

    2017-07-01

    Idiopathic pulmonary fibrosis (IPF) is an increasingly recognized, often fatal lung disease of unknown etiology. The aim of this study was to use whole-exome sequencing to improve understanding of the genetic architecture of pulmonary fibrosis. We performed a case-control exome-wide collapsing analysis including 262 unrelated individuals with pulmonary fibrosis clinically classified as IPF according to American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines (81.3%), usual interstitial pneumonia secondary to autoimmune conditions (11.5%), or fibrosing nonspecific interstitial pneumonia (7.2%). The majority (87%) of case subjects reported no family history of pulmonary fibrosis. We searched 18,668 protein-coding genes for an excess of rare deleterious genetic variation using whole-exome sequence data from 262 case subjects with pulmonary fibrosis and 4,141 control subjects drawn from among a set of individuals of European ancestry. Comparing genetic variation across 18,668 protein-coding genes, we found a study-wide significant (P RTEL1, and PARN. A model qualifying ultrarare, deleterious, nonsynonymous variants implicated TERT and RTEL1, and a model specifically qualifying loss-of-function variants implicated RTEL1 and PARN. A subanalysis of 186 case subjects with sporadic IPF confirmed TERT, RTEL1, and PARN as study-wide significant contributors to sporadic IPF. Collectively, 11.3% of case subjects with sporadic IPF carried a qualifying variant in one of these three genes compared with the 0.3% carrier rate observed among control subjects (odds ratio, 47.7; 95% confidence interval, 21.5-111.6; P = 5.5 × 10 -22 ). We identified TERT, RTEL1, and PARN-three telomere-related genes previously implicated in familial pulmonary fibrosis-as significant contributors to sporadic IPF. These results support the idea that telomere dysfunction is involved in IPF pathogenesis.

  20. Radiation pneumonitis and fibrosis

    International Nuclear Information System (INIS)

    Shopova, V.; Salovsky, P.; Dancheva, V.

    2001-01-01

    The likelihood of toxic pulmonary lesions development as the result of radiation therapy for pulmonary carcinoma and breast cancer is discussed. Two possible forms of radiation induced changes are described, namely: classical radiation pneumonitis (RP) terminating with lung fibrosis circumscribed in the radiation zone, and sporadic RP giving rise to bilateral lymphatic alveolitis and manifestations outside the irradiation field. Attention is called to the fact that chemotherapy augments the risk of toxic lung damage occurrence. A number of markers for early RP diagnosis, including lactate dehydrogenase activity, KL-6, procollagen III, transforming growth factor β, C-reactive protein and partial oxygen pressure are listed. Therapeutic possibilities in coping with RP and pulmonary fibrosis are assayed. Apart from the standard therapeutic approach using corticosteroids and azatioprin, ideas are set forth concerning the application of some antioxidants, angiotensin converting enzyme inhibitors and γ-interferon. It is pointed out that radiation pneumonitis and pulmonary fibrosis treatment has an essential practical bearing on life expectancy and quality of life in a great number of cancer patients. (author)

  1. Radiotherapy of breast fibrosis

    International Nuclear Information System (INIS)

    Heibel, J.H.

    1979-01-01

    In a retrospective study radiotherapy of breast fibrosis in hormone-treated men with histologically confirmed prostate carcinoma was examined. 10 patients had received hormones even before irradiation, 113 obtained hormone administration only after irradiation. The objective size of the glandular body and the overall size of the breast were measured with a special method developed by the author. 46 patients indicated complaints. With hypertrophic mamma and hypertrophic mamilla in 67 examined patients, 127 different symptoms resulted in total. Four patients of the group who had obtained hormones before irradiation, suffered from subjective symptoms. It resulted that radiotherapy of breast fibrosis carried out during hormone treatment is no gynecomastia prophylaxis, that already existent mamma hypertrophies are irreversible, but that existent sensations were notably reduced within 6 months after irradiation therapy. These results indicate the necessity of a radiotherapy of the mamma fibrosis before the hormone treatment is begun. Particularly in cases of higher operative risks, also the possibility of preferring radiotherapy to mastectomy should be fully utilized, in view of adequate or even better therapeutic results. (orig./MG) [de

  2. Cyclic Nucleotide Signalling in Kidney Fibrosis

    Directory of Open Access Journals (Sweden)

    Elisabeth Schinner

    2015-01-01

    Full Text Available Kidney fibrosis is an important factor for the progression of kidney diseases, e.g., diabetes mellitus induced kidney failure, glomerulosclerosis and nephritis resulting in chronic kidney disease or end-stage renal disease. Cyclic adenosine monophosphate (cAMP and cyclic guanosine monophosphate (cGMP were implicated to suppress several of the above mentioned renal diseases. In this review article, identified effects and mechanisms of cGMP and cAMP regarding renal fibrosis are summarized. These mechanisms include several signalling pathways of nitric oxide/ANP/guanylyl cyclases/cGMP-dependent protein kinase and cAMP/Epac/adenylyl cyclases/cAMP-dependent protein kinase. Furthermore, diverse possible drugs activating these pathways are discussed. From these diverse mechanisms it is expected that new pharmacological treatments will evolve for the therapy or even prevention of kidney failure.

  3. Serum markers of liver fibrosis

    DEFF Research Database (Denmark)

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

    2010-01-01

    -epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. METHODS: Pubmed was search for keywords; Liver fibrosis, neo......, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis....

  4. Accuracy of FibroScan for diagnosing liver fibrosis

    Directory of Open Access Journals (Sweden)

    Jian ZHANG

    2011-11-01

    Full Text Available Objective To evaluate the accuracy of transient elastometry(FibroScan for the detection of liver fibrosis.Methods A total of 323 patients diagnosed with chronic liver disease based on pathological examination in the 302 Hospital of the People’s Liberation Army from April to December of 2009 were involved in the current study.Among them,141 patients were subjected to liver biopsy.Their liver function,coagulant index,B-ultrasound and blood cell count were examined clinically.Four examinations related to liver fibrosis were done on some of the patients.Meanwhile,FibroScan was used for liver stiffness measurement(LSM of every patient.The correlation between liver stiffness and the serologic index and liver fibrosis degree was analyzed.The Receive Operating Characteristic(ROC curve was adopted to analyze the accuracy of FibroScan for diagnosing liver fibrosis.Results Each serologic index was significantly correlated with liver stiffness(P < 0.001,and liver stiffness was closely related to the stage of liver fibrosis(r=0.74,P < 0.001.The statistical results of the 141 patients who underwent pathologic examination show that the areas under the ROC curve were 0.97(0.94,1.00 for patients with portal fibrosis(F1,0.96(0.93,0.99 for patients with significant fibrosis(F2,0.99(0.98,1.00 for patients with severe fibrosis(F3,and 0.97(0.94,0.99 for patients with cirrhosis(F4.The cutoff values were 4.4KPa,6.8KPa,9.7KPa,and 10.0KPa,respectively.Conclusion FibroScan is valuable for the diagnosis of liver fibrosis.It can be used as the basis for follow-up and management of patients with chronic liver diseases.

  5. Dose rate constant and energy spectrum of interstitial brachytherapy sources

    International Nuclear Information System (INIS)

    Chen Zhe; Nath, Ravinder

    2001-01-01

    In the past two years, several new manufacturers have begun to market low-energy interstitial brachytherapy seeds containing 125 I and 103 Pd. Parallel to this development, the National Institute of Standards and Technology (NIST) has implemented a modification to the air-kerma strength (S K ) standard for 125 I seeds and has also established an S K standard for 103 Pd seeds. These events have generated a considerable number of investigations on the determination of the dose rate constants (Λ) of interstitial brachytherapy seeds. The aim of this work is to study the general properties underlying the determination of Λ and to develop a simple method for a quick and accurate estimation of Λ. As the dose rate constant of clinical seeds is defined at a fixed reference point, we postulated that Λ may be calculated by treating the seed as an effective point source when the seed's source strength is specified in S K and its source characteristics are specified by the photon energy spectrum measured in air at the reference point. Using a semi-analytic approach, an analytic expression for Λ was derived for point sources with known photon energy spectra. This approach enabled a systematic study of Λ as a function of energy. Using the measured energy spectra, the calculated Λ for 125 I model 6711 and 6702 seeds and for 192 Ir seed agreed with the AAPM recommended values within ±1%. For the 103 Pd model 200 seed, the agreement was 5% with a recently measured value (within the ±7% experimental uncertainty) and was within 1% with the Monte Carlo simulations. The analytic expression for Λ proposed here can be evaluated using a programmable calculator or a simple spreadsheet and it provides an efficient method for checking the measured dose rate constant for any interstitial brachytherapy seed once the energy spectrum of the seed is known

  6. Nephrogenic systemic fibrosis: history and epidemiology

    DEFF Research Database (Denmark)

    Thomsen, Henrik S

    2009-01-01

    Nephrogenic systemic fibrosis (NSF) is a new disease; the first case was diagnosed in 1997. It took 9 years before an association between NSF and gadolinium-based contrast agents (Gd-CAs) was identified. Gadolinium has several advantages for use in relation to enhanced MRI, but it is also a toxic...... that the real number of patients who have NSF has not been accurately totaled; the disease seems to be underdiagnosed for various reasons....

  7. Nutrient Status of Adults with Cystic Fibrosis

    Science.gov (United States)

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

    2011-01-01

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

  8. Persistence of ventilatory defect after resolution of pulmonary interstitial emphysema in a preterm baby.

    Science.gov (United States)

    Filho, Luiz Vicente Ferreira da Silva; Rossi, Felipe De Souza; Deutsch, Alice d'Agostini; Yagui, Ana Cristina Zanon; Timenetsky, Karina; Rebello, Celso de Moura

    2010-07-01

    Pulmonary interstitial emphysema is a common complication of mechanical ventilation in preterm babies. We report a case of severe unilateral pulmonary interstitial emphysema in a premature newborn, treated with high-frequency oscillatory ventilation, lateral decubitus positioning and selective intubation. After complete radiological resolution of the pulmonary emphysema in the left lung, the patient was studied by electrical impedance tomography and a marked reduction of ventilation was identified in the left lung despite radiological resolution of the cysts. This finding indicates that functional abnormalities may persist for longer periods after radiologic resolution of such lesions.

  9. Self-interstitials structure in the hcp metals: A further perspective from first-principles calculations

    Energy Technology Data Exchange (ETDEWEB)

    Pasianot, Roberto C., E-mail: pasianot@cnea.gov.ar [Gerencia Materiales, CAC-CNEA, Avda. Gral. Paz 1499, 1650 San Martín (Argentina); CONICET, Godoy Cruz 2290, 1425 Buenos Aires (Argentina); Instituto Sabato, UNSAM/CNEA, Avda. Gral. Paz 1499, 1650 San Martín (Argentina)

    2016-12-01

    We study the structure of several standard and non-standard self-interstitial configurations in a series of hcp metals, by using Density Functional Theory as embodied in the computer codes SIESTA and WIEN2k. The considered metals include Be, Mg, Ti, Zr, Co, Zn, and Cd, thus spanning the whole range of experimental c/a ratios, different kinds of bonding, and even magnetism (Co). The results show the importance of low symmetry configurations, closely related to the non-basal crowdion, in order to rationalize the experimental data on self-interstitial structure and migration.

  10. Subcutaneous fibrosis after whole neck irradiation

    International Nuclear Information System (INIS)

    Hirota, Saeko; Tsujino, Kayoko; Oshitani, Takashi; Hishikawa, Yoshio; Takada, Yoshiki; Kono, Michio; Abe, Mitsuyuki

    2002-01-01

    Purpose: To identify the risk factors for moderate to severe subcutaneous fibrosis after whole neck irradiation. Methods and Materials: We analyzed 233 cases of patients who had undergone whole neck irradiation with 4-MV X-ray or 8-10-MeV electrons, or both, and had been followed with regard to their skin condition for at least 1 year. The prescribed dose to the whole neck ranged from 19.2 to 72.4 Gy (median 50). The skin-absorbed dose was specified as that at a depth of 4.1 mm (d4.1-mm depth ), and a biologically equivalent dose (BED) of d4.1-mm depth was also estimated (BED 1.8 4.1-mm depth ). Results: Univariate analysis revealed that previous neck dissection, concurrent chemotherapy, corticosteroid administration as a part of chemotherapy, fractionation, and BED 1.8 4.1-mm depth were significant prognostic variables. Multivariate analysis showed that BED 1.8 4.1-mm depth and previous neck dissection were the only prognostic variables for moderate to severe subcutaneous fibrosis. Conclusion: A high dose to a 4.1-mm depth of the skin and a history of neck dissection were identified as the predominant risk factors for moderate to severe subcutaneous fibrosis after whole neck irradiation. A subcutaneous dose should be considered in radiotherapy treatment planning involving the whole neck, especially in cases in which patients have undergone previous neck dissection

  11. Childhood sexual trauma in women with interstitial cystitis/bladder pain syndrome

    DEFF Research Database (Denmark)

    Nickel, J Curtis; Tripp, Dean A; Pontari, Michel

    2011-01-01

    The impact of early lifetime trauma on symptom severity and quality of life of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) has not been fully elucidated. We wanted to determine and compare the prevalence and impact of childhood traumatic events, with an emphasis on childhood...... sexual abuse, on patient symptoms, quality of life and other biopsychosocial parameters....

  12. Childhood sexual trauma in women with interstitial cystitis/bladder pain syndrome

    DEFF Research Database (Denmark)

    Nickel, J Curtis; Tripp, Dean A; Pontari, Michel

    2011-01-01

    The impact of early lifetime trauma on symptom severity and quality of life of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) has not been fully elucidated. We wanted to determine and compare the prevalence and impact of childhood traumatic events, with an emphasis on childhood...

  13. Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    Colchicine is an anti-inflammatory and anti-fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine...... evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis....

  14. Relationship between the prognosis of interstitial pneumonia and its comorbidities

    International Nuclear Information System (INIS)

    Ando, Katsutoshi; Ohkuni, Yoshihiro; Makino, Hideki; Kawamura, Yasutaka; Motojima, Shinji; Kaneko, Norihiro

    2011-01-01

    To investigate the relationship between the prognosis of chronic interstitial pneumonia (IP) and its comorbidities, we conducted a retrospective study for clinically and radiologically diagnosed IP. We assessed comorbidities by using the Charlson Comorbidity Index (CCI). We classified 224 patients given clinical diagnoses of chronic IP (excluding the patients who had clear causes such as collagen disease, infection, drugs or radiation) in our institution between April 2000 and June 2010, into 2 groups; those with clinical diagnoses of idiopathic pulmonary fibrosis (IPF: 108 cases) and those with other chronic IP but without honeycomb lung (116 cases); and analyzed their backgrounds and comorbidities. We also classified them into survival and non-survival groups to assess their prognostic factors. Although the smoking status of patients with clinically diagnosed IPF was higher, and SpO2 was lower than those with other chronic IP without honeycomb lung, the mean age, comorbidities and CCI did not differ between them. The 5-year overall survival of the clinically-diagnosed IPF group was lower than that of the other chronic IP without honeycomb lung group (50.8% vs. 76.3%, p<0.01). In cases of other chronic IP without honeycomb lung, the CCI of non-survival cases was higher than that of survival cases (4.05 vs. 2.47, p<0.01), although patient backgrounds did not differ between survival and non-survival cases in those with clinically diagnosed IPF (CCI: 2.32 vs. 2.98, p=0.70). Our analysis revealed the possibility that comorbidities and CCI were prognostic factors in other chronic IP cases without honeycomb lung, although the prognosis of IPF was not affected by their comorbidity. (author)

  15. Inhaled mannitol for cystic fibrosis.

    Science.gov (United States)

    Nevitt, Sarah J; Thornton, Judith; Murray, Clare S; Dwyer, Tiffany

    2018-02-09

    Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review. To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 28 September 2017. All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment. Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE. Six studies (reported in 50 publications) were included with a total of 784 participants.Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were

  16. Pancreas tumor interstitial pressure catheter measurement

    Science.gov (United States)

    Nieskoski, Michael D.; Gunn, Jason; Marra, Kayla; Trembly, B. Stuart; Pogue, Brian W.

    2016-03-01

    This paper highlights the methodology in measuring interstitial pressure in pancreatic adenocarcinoma tumors. A Millar Mikrotip pressure catheter (SPR-671) was used in this study and a system was built to amplify and filter the output signal for data collection. The Millar pressure catheter was calibrated prior to each experiment in a water column at 37°C, range of 0 to 60 inH2O (112 mmHg), resulting in a calibration factor of 33 mV / 1 inH2O. The interstitial pressures measured in two orthotopically grown pancreatic adenocarcinoma tumor were 57 mmHg and 48 mmHg, respectively. Verteporfin uptake into the pancreatic adenocarcinoma tumor was measured using a probe-based experimental dosimeter.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  18. Fatal interstitial lung disease associated with icotinib

    OpenAIRE

    Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi; Chen, Rongchang

    2014-01-01

    The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, th...

  19. A case of idiopathic interstitial pneumonia

    OpenAIRE

    豊見山, 寛; 兼島, 洋; 下地, 克佳; 金城, 勇徳; 中富, 昌夫; 小張, 一峰; 松井, 克明; Tomiyama, Hiroshi; Kaneshima, Hiroshi; Shimoji, Katsuyoshi; Kinjo, Yutoku; Nakatomi, Masao; Kobari, Kazumine; Matsui, Katsuaki; 琉球大学医学部第一内科

    1982-01-01

    A case of idiopathic interstitial pneumonia was reported. A 53-year-old man was admitted to our hospital with his complaint of shortness of breath. On physical examination clubbing of the fingers was noticed and velcro rales was heard on the bilateral lower back. On laboratory data no remarkable finding was revealed. Chest roentgenogram showed diffuse reticulonodular shadow and small ring shadow of the bilateral lower lung fields. On pulmonary function test decline of VC and DLco was revealed...

  20. Self-interstitial atoms in metals

    International Nuclear Information System (INIS)

    Schilling, W.

    1978-01-01

    The present state of knowledge and understanding of the properties of self-interstitial atoms (SIAs) in metals is reviewed. Special emphasis is given to a discussion of the structure of SIAs and those properties which relate to structure such as relaxation volumes, elastic polarizabilities, defect vibrations, geometry of jump processes, and elastic interactions. The present experimental status with respect to these properties is summarized, and the basic theoretical concepts for their understanding are presented as simply as possible. (Auth.)

  1. Development of an interstitial cystitis risk score for bladder permeability.

    Directory of Open Access Journals (Sweden)

    Laura E Lamb

    Full Text Available Interstitial cystitis/bladder pain syndrome (IC is a multifactorial syndrome of severe pelvic and genitalia pain and compromised urinary function; a subset of IC patients present with Hunner's lesions or ulcers on their bladder walls (UIC. UIC is diagnosed by cystoscopy, which may be quite painful. The objective of this study was to determine if a calculated Bladder Permeability Defect Risk Score (BP-RS based on non-invasive urinary cytokines could discriminate UIC patients from controls and IC patients without Hunner's ulcers.A national crowdsourcing effort targeted IC patients and age-matched controls to provide urine samples. Urinary cytokine levels for GRO, IL-6, and IL-8 were determined using a Luminex assay.We collected 448 urine samples from 46 states consisting of 153 IC patients (147 female, 6 male, of which 54 UIC patients (50 females, 4 male, 159 female controls, and 136 male controls. A defined BP-RS was calculated to classify UIC, or a bladder permeability defect etiology, with 89% validity.The BP-RS Score quantifies UIC risk, indicative of a bladder permeability defect etiology in a subset of IC patients. The Bladder Permeability Defect Risk Score is the first validated urine biomarker assay for interstitial cystitis/bladder pain syndrome.

  2. Temperature control in interstitial laser cancer immunotherapy

    Science.gov (United States)

    Bandyopadhyay, Pradip K.; Holmes, Kyland; Burnett, Corinthius; Zharov, Vladimir P.

    2003-07-01

    Positive results of Laser-Assisted Cancer Immunotherapy (LACI) have been reported previously in the irradiation of superficial tumors. This paper reports the effect of LACI using laser interstitial therapy approach. We hypothesize that the maximum immuno response depends on laser induced tumor temperature. The measurement of tumor temperature is crucial to ensure necrosis by thermal damage and immuno response. Wister Furth female rats in this study were inoculated with 13762 MAT B III rat mammary adinocarcinoma. LACI started seven to ten days following inoculation. Contrary to surface irradation, we applied laser interstitial irradiation of tumor volume to maximize the energy deposition. A diode laser with a wavelength of 805 nm was used for tumor irradiation. The laser energy was delivered inside the tumor through a quartz fiber. Tumor temperature was measured with a micro thermocouple (interstitial), while the tumor surface temperature was controlled with an IR detector. The temperature feedback demonstrates that it is possible to maintain the average tumor temperature at the same level with reasonable accuracy in the desired range from 65°C-85°C. In some experiments we used microwave thermometry to control average temperature in deep tissue for considerable period of time, to cause maximum thermal damage to the tumor. The experimental set-up and the different temperature measurement techniques are reported in detail, including the advantages and disadvantages for each method.

  3. Nature of interstitially induced lattice strains

    International Nuclear Information System (INIS)

    Emin, D.

    1978-01-01

    The addition of interstitial atoms to a metal lattice has been likened to the addition of extra billiard balls to an array of tangentially touching billiard balls. In such a picture the increased clustering of interstitials can lead to the buildup of larger and larger strain fields which ultimately are associated with the production of broken bonds. Simple models of the strain fields associated with the addition of particles to a lattice in which the force exerted between the added atoms and host atoms is finite have been studied. From these studies one can define situations in which the billiard-ball approach has qualitative validity and those in which it is inappropriate. Basically, those situations in which the displacements of the host atoms can be represented as involving acoustic phonons yield long-range strain fields analogous to those of the billiard-ball model with the radius of the extra billiard ball being determined by the stiffness of the host lattice and the forces between the added atom and the surrounding host atoms. If the displacements produced by the added atoms are represented as involving primarily optical phonons the displacement pattern is short-ranged and not described by the usual elasticity theory. For example, Vegard's law does not apply in these instances. Such concerns arise in considering the strains induced by interstitial helium in tritides

  4. Role of interstitial implantation in gynecological cancer

    International Nuclear Information System (INIS)

    Nori, D.; Hilaris, B.S.

    1987-01-01

    Recurrent cancer at any site carries a gloomy prognosis. Cancer of the cervix that recurs after radical surgery or curative radiation therapy is a perplexing problem confronting both gynecological and radiation oncologists. In the authors' series, 45% of the patients survived disease-free at 1 year and 10% survived without disease at 5 years or longer following interstitial implantation for recurrent cervical cancer. The optimal utilization of this procedure seems to depend on the site of recurrence, the extent of the disease in the pelvis, and the status of para-aortic node involvement. This retrospective analysis enabled the authors to identify the prognostic factors. The most favorable group benefited by this technique were those who presented with either central recurrence or unilateral, localized pelvic side wall recurrent disease. The least morbidity was noticed in those patients with minimal surgical manipulations at the time of the interstitial implantation. The authors recommended that only a limited and essential surgical procedure should accompany interstitial implantation, since the associated morbidity and mortality is high and survival brief

  5. Interstitial prostate brachytherapy. LDR-PDR-HDR

    International Nuclear Information System (INIS)

    Kovacs, Gyoergy; Hoskin, Peter

    2013-01-01

    The first comprehensive overview of interstitial brachytherapy for the management of local or locally advanced prostate cancer. Written by an interdisciplinary team who have been responsible for the successful GEC-ESTRO/EAU Teaching Course. Discusses in detail patient selection, the results of different methods, the role of imaging, and medical physics issues. Prostate brachytherapy has been the subject of heated debate among surgeons and the proponents of the various brachytherapy methods. This very first interdisciplinary book on the subject provides a comprehensive overview of innovations in low dose rate (LDR), high dose rate (HDR), and pulsed dose rate (PDR) interstitial brachytherapy for the management of local or locally advanced prostate cancer. In addition to detailed chapters on patient selection and the use of imaging in diagnostics, treatment guidance, and implantation control, background chapters are included on related medical physics issues such as treatment planning and quality assurance. The results obtained with the different treatment options and the difficult task of salvage treatment are fully discussed. All chapters have been written by internationally recognized experts in their fields who for more than a decade have formed the teaching staff responsible for the successful GEC-ESTRO/EAU Prostate Brachytherapy Teaching Course. This book will be invaluable in informing residents and others of the scientific background and potential of modern prostate brachytherapy. It will also prove a useful source of up-to-date information for those who specialize in prostate brachytherapy or intend to start an interstitial brachytherapy service.

  6. Imaging from cystic fibrosis

    International Nuclear Information System (INIS)

    Schmidt, H.; Posselt, H.G.

    2008-01-01

    Cystic fibrosis (CF) is the most frequent metabolic disorder with autosomal recessive inheritance in the Caucasian population. The gene defect is located on the long arm of chromosome 7. In Germany today, the actual median survival is 37 years. The genetic defect caused by chloride anion disturbances affects multiple body systems but the morbidity and mortality is due to lung disease. The secretion of highly viscous mucus promotes viral and bacterial pulmonary infections leading to airway obstruction and consecutive destruction of the lung parenchyma. This article will review and discuss both the clinical aspects of the disease and the diagnostic methods, referring in particular to new imaging strategies. (orig.)

  7. Thin-slice high-resolution CT study of pulmonary asbestosis and idiopathic interstitial pneumonia

    International Nuclear Information System (INIS)

    Hatakeyama, Masayuki; Maeda, Munehiro; Ohmura, Takuya

    1987-01-01

    Thin-slice high-resolution CT findings were compared between 36 patients with pulmonary asbestos exposure (AS) and 33 patients with idiopathic interstitial pneumonia (IIP). The CT scans of these patients were classified into 5 types (0-IV) by the subpleural curvilinear shadow (SCLS) and honey-comb shadow (HS). SCLS was detected in 22 (62 %) patients with AS and 7 (21 %) with IIP. HS was detected in 14 (39 %) patients with AS and 33 (100 %) with IIP. In both the diseases, SCLS was distributed mainly in the lower lobe in CT types I and II, and in mildly fibrotic segments in types III and IV. In CT types II, III and IV, SCLS was always communicated with HS. Thin-slice high-resolution CT is considered very helpful in diagnosis and staging of not only AS and IIP but also pulmonary fibrosis. (author)

  8. Chymase: a multifunctional player in pulmonary hypertension associated with lung fibrosis.

    Science.gov (United States)

    Kosanovic, Djuro; Luitel, Himal; Dahal, Bhola Kumar; Cornitescu, Teodora; Janssen, Wiebke; Danser, A H Jan; Garrelds, Ingrid M; De Mey, Jo G R; Fazzi, Gregorio; Schiffers, Paul; Iglarz, Marc; Fischli, Walter; Ghofrani, Hossein Ardeschir; Weissmann, Norbert; Grimminger, Friedrich; Seeger, Werner; Reiss, Irwin; Schermuly, Ralph Theo

    2015-10-01

    Limited literature sources implicate mast-cell mediator chymase in the pathologies of pulmonary hypertension and pulmonary fibrosis. However, there is no evidence on the contribution of chymase to the development of pulmonary hypertension associated with lung fibrosis, which is an important medical condition linked with increased mortality of patients who already suffer from a life-threatening interstitial lung disease.The aim of this study was to investigate the role of chymase in this particular pulmonary hypertension form, by using a bleomycin-induced pulmonary hypertension model.Chymase inhibition resulted in attenuation of pulmonary hypertension and pulmonary fibrosis, as evident from improved haemodynamics, decreased right ventricular remodelling/hypertrophy, pulmonary vascular remodelling and lung fibrosis. These beneficial effects were associated with a strong tendency of reduction in mast cell number and activity, and significantly diminished chymase expression levels. Mechanistically, chymase inhibition led to attenuation of transforming growth factor β1 and matrix-metalloproteinase-2 contents in the lungs. Furthermore, chymase inhibition prevented big endothelin-1-induced vasoconstriction of the pulmonary arteries.Therefore, chymase plays a role in the pathogenesis of pulmonary hypertension associated with pulmonary fibrosis and may represent a promising therapeutic target. In addition, this study may provide valuable insights on the contribution of chymase in the pulmonary hypertension context, in general, regardless of the pulmonary hypertension form. Copyright ©ERS 2015.

  9. Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

    Science.gov (United States)

    Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

    2015-03-01

    Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

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

    Directory of Open Access Journals (Sweden)

    Trawinska MA

    2016-04-01

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

  11. Connective matrix organization in human pulmonary fibrosis. Collagen polymorphism analysis in fibrotic deposits by immunohistological methods.

    Science.gov (United States)

    Takiya, C; Peyrol, S; Cordier, J F; Grimaud, J A

    1983-01-01

    In the interstitium of the alveolar septa in the peripheral parts of the lung, four molecular types of collagen (I, III, IV and V) each with different morphological appearances, can be identified. The structural integrity of collagens accounts for the physiological efficiency of the lung. Fibrous thickening of alveolar septa is an invariable result of various diseases affecting the interstitium of the lung. The light and electron microscopic findings, and the immunological typing of collagens in six cases of fibrotic alveolar disease, are described. In the alveolar septa, two different compartments (the alveolo-capillary junction and the supportive axis) were affected by fibrosis: the alveolo-capillary junction was widened by the addition of interstitial collagens to basement membranes. In the axis, the increase of interstitial (types I and III) collagen gave rise to different patterns of connective matrix organization, graded as Loose or Dense depending on quantitative alterations of the type I/III ratio. The mode of organization of the fibrotic lung connective matrix, which depends on the quality of deposits in the matrix, may be correlated with the evolution of interstitial pulmonary fibrosis, in terms of its stability, remodelling ability and reversibility.

  12. Serial automated quantitative CT analysis in idiopathic pulmonary fibrosis. Functional correlations and comparison with changes in visual CT scores

    International Nuclear Information System (INIS)

    Jacob, Joseph; Bartholmai, Brian J.; Rajagopalan, Srinivasan; Kokosi, Maria; Wells, Athol U.; Egashira, Ryoko; Brun, Anne Laure; Nair, Arjun; Walsh, Simon L.F.; Karwoski, Ronald

    2018-01-01

    To determine whether computer-based CT quantitation of change can improve on visual change quantification of parenchymal features in IPF. Sixty-six IPF patients with serial CT imaging (6-24 months apart) had CT features scored visually and with a computer software tool: ground glass opacity, reticulation and honeycombing (all three variables summed as interstitial lung disease extent [ILD]) and emphysema. Pulmonary vessel volume (PVV) was estimated by computer only. Relationships between changes in CT features and forced vital capacity (FVC) were examined using univariate and multivariate linear regression analyses. On univariate analysis, changes in computer variables demonstrated stronger linkages to FVC change than changes in visual scores (CALIPER ILD:R 2 =0.53, p<0.0001; Visual ILD:R 2 =0.16, p=0.001). PVV increase correlated most strongly with relative FVC change (R 2 =0.57). When PVV constituents (vessel size and location) were examined, an increase in middle zone vessels linked most strongly to FVC decline (R 2 =0.57) and was independent of baseline disease severity (characterised by CT fibrosis extent, FVC, or DLco). An increase in PVV, specifically an increase in middle zone lung vessels, was the strongest CT determinant of FVC decline in IPF and was independent of baseline disease severity. (orig.)

  13. Serial automated quantitative CT analysis in idiopathic pulmonary fibrosis. Functional correlations and comparison with changes in visual CT scores

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, Joseph; Bartholmai, Brian J.; Rajagopalan, Srinivasan [Mayo Clinic Rochester, Division of Radiology, Rochester, MN (United States); Kokosi, Maria; Wells, Athol U. [Royal Brompton and Harefield NHS Foundation Trust, Interstitial Lung Disease Unit, Royal Brompton Hospital, London (United Kingdom); Egashira, Ryoko [Saga Daigaku, Department of Radiology, Saga (Japan); Brun, Anne Laure [Whittington Hospital, Department of Radiology, London (United Kingdom); Nair, Arjun [Guys and St Thomas' NHS Foundation Trust, Department of Radiology, London (United Kingdom); Walsh, Simon L.F. [Kings College Hospital NHS Foundation Trust, Department of Radiology, London (United Kingdom); Karwoski, Ronald [Mayo Clinic Rochester, Department of Physiology and Biomedical Engineering, Rochester, MN (United States)

    2018-03-15

    To determine whether computer-based CT quantitation of change can improve on visual change quantification of parenchymal features in IPF. Sixty-six IPF patients with serial CT imaging (6-24 months apart) had CT features scored visually and with a computer software tool: ground glass opacity, reticulation and honeycombing (all three variables summed as interstitial lung disease extent [ILD]) and emphysema. Pulmonary vessel volume (PVV) was estimated by computer only. Relationships between changes in CT features and forced vital capacity (FVC) were examined using univariate and multivariate linear regression analyses. On univariate analysis, changes in computer variables demonstrated stronger linkages to FVC change than changes in visual scores (CALIPER ILD:R{sup 2}=0.53, p<0.0001; Visual ILD:R{sup 2}=0.16, p=0.001). PVV increase correlated most strongly with relative FVC change (R{sup 2}=0.57). When PVV constituents (vessel size and location) were examined, an increase in middle zone vessels linked most strongly to FVC decline (R{sup 2}=0.57) and was independent of baseline disease severity (characterised by CT fibrosis extent, FVC, or DLco). An increase in PVV, specifically an increase in middle zone lung vessels, was the strongest CT determinant of FVC decline in IPF and was independent of baseline disease severity. (orig.)

  14. Experimental depletion of different renal interstitial cell populations

    International Nuclear Information System (INIS)

    Bohman, S.O.; Sundelin, B.; Forsum, U.; Tribukait, B.

    1988-01-01

    To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

  15. Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings.

    Science.gov (United States)

    Maglione, Paul J; Overbey, Jessica R; Cunningham-Rundles, Charlotte

    2015-01-01

    Common variable immunodeficiency may be complicated by interstitial lung disease, which leads to worsened morbidity and mortality in some. Although immunomodulatory treatment has efficacy, choice of patient, duration of treatment, and long-term follow-up are not available. Interstitial lung disease appears stable in certain instances, so it is not known whether all patients will develop progressive disease or require immunomodulatory therapy. This study aims to determine if all common variable immunodeficiency patients with interstitial lung disease have physiological worsening, and if clinical and/or laboratory parameters may correlate with disease progression. A retrospective review of medical records at Mount Sinai Medical Center in New York was conducted for referred patients with common variable immunodeficiency, CT scan-confirmed interstitial lung disease, and periodic pulmonary function testing covering 20 or more months before immunomodulatory therapy. Fifteen patients were identified from the retrospective review and included in this study. Of the 15 patients with common variable immunodeficiency, 9 had physiological worsening of interstitial lung disease adapted from consensus guidelines, associated with significant reductions in forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of the lung for carbon monoxide. Those with progressive lung disease also had significantly lower mean immunoglobulin G levels, greater increases and highest levels of serum immunoglobulin M (IgM), and more significant thrombocytopenia. Interstitial lung disease resulted in physiological worsening in many, but not all subjects, and was associated with suboptimal immunoglobulin G replacement. Those with worsening pulmonary function tests, elevated IgM, and severe thrombocytopenic episodes appear to be at highest risk for progressive disease. Such patients may benefit from immunomodulatory treatment. Copyright © 2015 American Academy of Allergy

  16. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    International Nuclear Information System (INIS)

    Hwang, Kyu Won; Woo, Ok Hee; Yong, Hwan Seok; Shin, Bong Kyung; Shim, Jae Jeong; Kang, Eun Young

    2008-01-01

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

  17. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Kyu Won; Woo, Ok Hee; Yong, Hwan Seok; Shin, Bong Kyung; Shim, Jae Jeong; Kang, Eun Young [College of Medicine, Korea University, Guro Hospital, Seoul (Korea, Republic of)

    2008-04-15

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

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

    Directory of Open Access Journals (Sweden)

    I.V. Martynova

    2011-01-01

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

  19. Physical exercise training for cystic fibrosis.

    Science.gov (United States)

    Radtke, Thomas; Nevitt, Sarah J; Hebestreit, Helge; Kriemler, Susi

    2017-11-01

    Physical exercise training may form an important part of regular care for people with cystic fibrosis. This is an update of a previously published review. To assess the effects of physical exercise training on exercise capacity by peak oxygen consumption, pulmonary function by forced expiratory volume in one second, health-related quality of life and further important patient-relevant outcomes in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 04 May 2017.We searched ongoing trials registers (clinicaltrials.gov and the WHO ICTRP). Date of most recent search: 10 August 2017. All randomised and quasi-randomised controlled clinical trials comparing exercise training of any type and a minimum duration of two weeks with conventional care (no training) in people with cystic fibrosis. Two authors independently selected studies for inclusion, assessed methodological quality and extracted data. The quality of the evidence was assessed using the GRADE system. Of the 83 studies identified, 15 studies which included 487 participants, met the inclusion criteria. The numbers in each study ranged from nine up to 72 participants; two studies were in adults, seven were in children and adolescents and six studies included all age ranges. Four studies of hospitalised participants lasted less than one month and 11 studies were outpatient-based, lasting between two months and three years. The studies included participants with a wide range of disease severity and employed differing levels of supervision with a mixture of types of training. There was also wide variation in the quality of the included studies.This systematic review shows very low- to low-quality evidence from both short- and long-term studies that in people

  20. Clinical and economic burden of idiopathic pulmonary fibrosis in Quebec, Canada.

    Science.gov (United States)

    Tarride, Jean-Eric; Hopkins, Robert B; Burke, Natasha; Guertin, Jason R; O'Reilly, Daria; Fell, Charlene D; Dion, Genevieve; Kolb, Martin

    2018-01-01

    Idiopathic pulmonary fibrosis (IPF), although rare, is a severe and costly disease. To estimate the clinical and economic burden of IPF over multiple years before and after diagnosis using comprehensive administrative databases for the province of Quebec, Canada. Several administrative databases from Quebec, providing information on hospital care, community care, and pharmaceuticals, were linked over a 5-year period ending March 31, 2011, which was before approval of antifibrotic drugs in Canada. Prevalent and incident IPF cases were defined using International Classification Disease-10-CA codes and International Classification Disease-9-CM codes. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases and a narrow definition that required further diagnostic testing to confirm IPF diagnosis. Incident cases had an IPF code in a particular year without any IPF code in the 2 previous years. Health care resource utilization before and after the index diagnosis date was determined and costs calculated. Costs were expressed in 2016 Canadian dollars. Over 5-years, 10,579 (mean age: 76.4; 58% male) satisfied the broad definition of IPF and 8,683 (mean age: 74.5; 57% male) satisfied the narrow definition (82% of broad). Incidences of IPF overall were 25.8 and 21.7/100,000 population for broad and narrow definitions, respectively. Three-year survival was 40% and 37% in broad and narrow cohorts, respectively. For both cohorts, health care resource utilization and costs increased several years before diagnosis ($2,721 and $7,049/patient 5 years and 2 years prior to diagnosis using a broad definition, respectively) and remained elevated for multiple years post diagnosis ($12,978 and $8,267 at 2 and 3 years postdiagnosis). Health care resource utilization and costs of IPF increase many years prior to diagnosis. Incorporating multiyear annual costs before and after diagnosis results in a higher estimate of the economic burden

  1. Exertional dyspnoea in interstitial lung diseases: the clinical utility of cardiopulmonary exercise testing

    Directory of Open Access Journals (Sweden)

    Matteo Bonini

    2017-02-01

    Full Text Available Interstitial lung diseases (ILDs represent a heterogeneous group of pathologies characterised by alveolar and interstitial damage, pulmonary inflammation (usually associated with fibrosis, decreased lung function and impaired gas exchange, which can be attributed to either a known or an unknown aetiology. Dyspnoea is one of the most common and disabling symptoms in patients with ILD, significantly impacting quality of life. The mechanisms causing dyspnoea are complex and not yet fully understood. However, it is recognised that dyspnoea occurs when there is an imbalance between the central respiratory efferent drive and the response of the respiratory musculature. The respiratory derangement observed in ILD patients at rest is even more evident during exercise. Pathophysiological mechanisms responsible for exertional dyspnoea and reduced exercise tolerance include altered respiratory mechanics, impaired gas exchange, cardiovascular abnormalities and peripheral muscle dysfunction. This review describes the respiratory physiology of ILD, both at rest and during exercise, and aims to provide comprehensive and updated evidence on the clinical utility of the cardiopulmonary exercise test in the assessment and management of these pathological entities. In addition, the role of exercise training and pulmonary rehabilitation programmes in the ILD population is addressed.

  2. Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts

    International Nuclear Information System (INIS)

    Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.; Huang, J.-S.

    2010-01-01

    Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and α-smooth muscle actin (α-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.

  3. Do We Need Exercise Tests to Detect Gas Exchange Impairment in Fibrotic Idiopathic Interstitial Pneumonias?

    Directory of Open Access Journals (Sweden)

    Benoit Wallaert

    2012-01-01

    Full Text Available In patients with fibrotic idiopathic interstitial pneumonia (f-IIP, the diffusing capacity for carbon monoxide (DLCO has been used to predict abnormal gas exchange in the lung. However, abnormal values for arterial blood gases during exercise are likely to be the most sensitive manifestations of lung disease. The aim of this study was to compare DLCO, resting PaO2, P(A-aO2 at cardiopulmonary exercise testing peak, and oxygen desaturation during a 6-min walk test (6MWT. Results were obtained in 121 patients with idiopathic pulmonary fibrosis (IPF, n=88 and fibrotic nonspecific interstitial pneumonias (NSIP, n=33. All but 3 patients (97.5% had low DLCO values (35 mmHg and 100 (83% demonstrated significant oxygen desaturation during 6MWT (>4%. Interestingly 27 patients had low DLCO and normal P(A-aO2, peak and/or no desaturation during the 6MWT. The 3 patients with normal DLCO also had normal PaO2, normal P(A-aO2, peak, and normal oxygen saturation during 6MWT. Our results demonstrate that in fibrotic IIP, DLCO better defines impairment of pulmonary gas exchange than resting PaO2, exercise P(A-aO2, peak, or 6MWT SpO2.

  4. Mucin 5B promoter polymorphism is associated with susceptibility to interstitial lung diseases in Chinese males.

    Directory of Open Access Journals (Sweden)

    Chunli Wang

    Full Text Available The variation of G>T in the MUC5B promoter (rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF and familial interstitial pneumonia (FIP in Caucasians, but no information is available regarding this variant in the Chinese population. We recruited 405 patients with interstitial lung diseases (ILD, including 165 IPF patients and 2043 healthy controls, for genotyping the MUC5B gene in the Chinese population. One hundred three patients with pneumonia and 360 patients with autoimmune diseases (ADs were recruited as disease controls. Our results indicated that the prevalence of the minor allele (T of the polymorphism rs35705950 in healthy Chinese subjects was approximately 0.66%, which was lower than that described in the Caucasian population. The frequencies of the T allele were 3.33% and 2.22% in IPF and ILD patients, respectively, and these values were significantly higher than those of healthy controls (P = 0.001, OR = 4.332 for IPF, and P = 0.002, OR = 2.855 for ILD. A stratified analysis showed that this variant in MUC5B associated with the risk for ILD mainly in older male Chinese subjects. No difference was observed between patients with pneumonia, AD patients, and healthy controls.

  5. Rare variants in RTEL1 are associated with familial interstitial pneumonia.

    Science.gov (United States)

    Cogan, Joy D; Kropski, Jonathan A; Zhao, Min; Mitchell, Daphne B; Rives, Lynette; Markin, Cheryl; Garnett, Errine T; Montgomery, Keri H; Mason, Wendi R; McKean, David F; Powers, Julia; Murphy, Elissa; Olson, Lana M; Choi, Leena; Cheng, Dong-Sheng; Blue, Elizabeth Marchani; Young, Lisa R; Lancaster, Lisa H; Steele, Mark P; Brown, Kevin K; Schwarz, Marvin I; Fingerlin, Tasha E; Schwartz, David A; Lawson, William E; Loyd, James E; Zhao, Zhongming; Phillips, John A; Blackwell, Timothy S

    2015-03-15

    Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (RTEL1 function. Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis.

  6. Thoracic periaortal fibrosis and Ormond's disease

    International Nuclear Information System (INIS)

    Kacl, G.M.; Bino, M.; Salomon, F.; Risti, B.; Marincek, B.

    1995-01-01

    Two cases of thoracic periaortal fibrosis as a manifestation of retroperitoneal fibrosis (Ormond's disease) are shown on CT and MRI. Thoracic periaortal fibrosis can result in an inflammatory aneurysmo with chronic dissection. Manifestation of thoracic periaortal fibrosis may typically occur intermittently over decades. (orig.) [de

  7. Cystic fibrosis: a clinical view.

    Science.gov (United States)

    Castellani, Carlo; Assael, Baroukh M

    2017-01-01

    Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.

  8. Interstitial Lung Disease in Rheumatoid Arthritis in the Era of Biologics

    Directory of Open Access Journals (Sweden)

    A. Picchianti Diamanti

    2011-01-01

    Full Text Available Interstitial lung disease (ILD represents a severe manifestation in connective tissue diseases (CTD, with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA, observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.

  9. Diagnostic accuracy of computed tomography and histopathology in the diagnosis of usual interstitial pneumonia

    International Nuclear Information System (INIS)

    Aaloekken, Trond Mogens; Mynarek, Georg; Kolbenstvedt, Alf; Naalsund, Anne; Elnaes Berstad, Audun; Solberg, Steinar; Stroem, Erik H.; Scott, Helge; Soeyseth, Vidar

    2012-01-01

    Background: The relative clinical benefit of histopathology and computed tomography (CT) in patients with idiopathic interstitial pneumonia (IIP) is under debate. Purpose: To analyze thin-section CT features and histopathologic findings in patients with usual interstitial pneumonia (UIP) in the clinical context of idiopathic pulmonary fibrosis (IPF), and to evaluate and compare diagnostic accuracy of the two methods among patients with an appropriate spectrum of IIP. Material and Methods: The study included 91 patients (49 men; mean age 53.2 years; median follow-up 7.2 years) with clinically suspected interstitial lung disease. All underwent surgical lung biopsy and thin-section CT. Two independent readers retrospectively assessed the CT images for the extent and pattern of abnormality and made a first-choice diagnosis. Two pathologists retrospectively assessed the histopathologic slides. In 64 patients with IIP, a retrospective composite reference standard identified 41 patients with UIP. CT characteristics of UIP and IIPs other than UIP were compared with univariate and multivariate analyses. Results: There was good agreement between the readers for the correct first-choice CT diagnosis of UIP (κ = 0.79). The sensitivity, specificity, and positive predictive value of the CT diagnosis of UIP were 63%, 96%, and 96%, respectively. The sensitivity, specificity, and positive predictive value of the histological diagnosis of UIP were 73%, 74%, and 83%, respectively. The CT feature that best differentiated UIP from IIPs other than UIP was the extent of reticular pattern (odds ratio, 5.1). Conclusion: Surgical lung biopsy may not be warranted in patients with thin-section CT diagnosis of UIP

  10. Diagnostic accuracy of computed tomography and histopathology in the diagnosis of usual interstitial pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Aaloekken, Trond Mogens; Mynarek, Georg; Kolbenstvedt, Alf (Dept. of Radiology, Oslo Univ. Hospital Rikshospitalet, Oslo (Norway)), Email: trond.mogens.aalokken@rikshospitalet.no; Naalsund, Anne (Dept. of Pulmonology, Oslo Univ. Hospital Rikshospitalet (Norway)); Elnaes Berstad, Audun (Dept. of Radiology, Oslo Univ. Hospital Rikshospitalet, Oslo (Norway); Univ. of Oslo (Norway)); Solberg, Steinar (Dept. of Thoracic Surgery, Oslo Univ. Hospital Rikshospitalet (Norway)); Stroem, Erik H.; Scott, Helge (Dept. of Pathology, Oslo Univ. Hospital Rikshospitalet (Norway)); Soeyseth, Vidar (Univ. of Oslo (Norway); Depts. of Pulmonology, Akershus Univ. Hospital, Loerenskog (Norway))

    2012-04-15

    Background: The relative clinical benefit of histopathology and computed tomography (CT) in patients with idiopathic interstitial pneumonia (IIP) is under debate. Purpose: To analyze thin-section CT features and histopathologic findings in patients with usual interstitial pneumonia (UIP) in the clinical context of idiopathic pulmonary fibrosis (IPF), and to evaluate and compare diagnostic accuracy of the two methods among patients with an appropriate spectrum of IIP. Material and Methods: The study included 91 patients (49 men; mean age 53.2 years; median follow-up 7.2 years) with clinically suspected interstitial lung disease. All underwent surgical lung biopsy and thin-section CT. Two independent readers retrospectively assessed the CT images for the extent and pattern of abnormality and made a first-choice diagnosis. Two pathologists retrospectively assessed the histopathologic slides. In 64 patients with IIP, a retrospective composite reference standard identified 41 patients with UIP. CT characteristics of UIP and IIPs other than UIP were compared with univariate and multivariate analyses. Results: There was good agreement between the readers for the correct first-choice CT diagnosis of UIP (kappa = 0.79). The sensitivity, specificity, and positive predictive value of the CT diagnosis of UIP were 63%, 96%, and 96%, respectively. The sensitivity, specificity, and positive predictive value of the histological diagnosis of UIP were 73%, 74%, and 83%, respectively. The CT feature that best differentiated UIP from IIPs other than UIP was the extent of reticular pattern (odds ratio, 5.1). Conclusion: Surgical lung biopsy may not be warranted in patients with thin-section CT diagnosis of UIP

  11. False negative newborn screen and neonatal cholestasis in a premature child with cystic fibrosis

    NARCIS (Netherlands)

    Heidendael, J. F.; Tabbers, M. M.; de Vreede, I.

    2014-01-01

    Newborn screening for cystic fibrosis enables early diagnosis and treatment, leading to better outcomes for patients with cystic fibrosis. Although the sensitivity of several screening protocols is high, false negative screening results of the newborn patient still occur, which can lead to a

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

    Science.gov (United States)

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

    2005-03-01

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

  13. Evolution of anisotropy in bcc Fe distorted by interstitial boron

    Science.gov (United States)

    Gölden, Dominik; Zhang, Hongbin; Radulov, Iliya; Dirba, Imants; Komissinskiy, Philipp; Hildebrandt, Erwin; Alff, Lambert

    2018-01-01

    The evolution of magnetic anisotropy in bcc Fe as a function of interstitial boron atoms was investigated in thin films grown by molecular beam epitaxy. The thermodynamic nonequilibrium conditions during film growth allowed one to stabilize an interstitial boron content of about 14 at .% accompanied by lattice tetragonalization. The c /a ratio scaled linearly with the boron content up to a maximum value of 1.05 at 300 °C substrate growth temperature, with a room-temperature magnetization of. In contrast to nitrogen interstitials, the magnetic easy axis remained in-plane with an anisotropy of approximately -5.1 ×106erg /cm3 . Density functional theory calculations using the measured lattice parameters confirm this value and show that boron local ordering indeed favors in-plane magnetization. Given the increased temperature stability of boron interstitials as compared to nitrogen interstitials, this study will help to find possible ways to manipulate boron interstitials into a more favorable local order.

  14. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    International Nuclear Information System (INIS)

    Van Beneden, Katrien; Geers, Caroline; Pauwels, Marina; Mannaerts, Inge; Wissing, Karl M.; Van den Branden, Christiane; Grunsven, Leo A. van

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation

  15. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: lvgrunsv@vub.ac.be [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  16. An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features

    Science.gov (United States)

    2014-01-01

    Background Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. Methods Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. Results All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema

  17. A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis.

    Science.gov (United States)

    Calès, Paul; Boursier, Jérôme; Oberti, Frédéric; Moal, Valérie; Fouchard Hubert, Isabelle; Bertrais, Sandrine; Hunault, Gilles; Rousselet, Marie Christine

    2018-04-01

    Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis-stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi-FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeter V2G ) with those of a test targeted for cirrhosis (CirrhoMeter V2G ). In the derivation CHC population, we first compared Multi-FibroMeter V2G to FibroMeter V2G and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis-stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeter V2G and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi-FibroMeter V2G and FibroMeter V2G were the following: cirrhosis AUROC, 0.906 versus 0.878 ( P fibrosis AUROC, 0.833 versus 0.832 ( P = 0.366). Multi-FibroMeter V2G had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates

  18. [Endocrine complications of cystic fibrosis in childhood].

    Science.gov (United States)

    Castanet, M; Wieliczko, M-C

    2012-05-01

    Since the 20 last years, the median age of survival has dramatically improved in children suffering from cystic fibrosis and complications such as growth retardation, pubertal delay and low bone mineral density are now more often than not observed in affected adolescents. The severity of the disease and the poor nutritional status due to pancreatic insufficiency and malabsorption are commonly implicated but recent data suggest that the disease could also play a role though the alteration of the chlore chanel (CFTR). Furthermore an increase prevalence of glucose intolerance and diabetes due to the progressive β cells destruction is observed in these children that make the life sometimes difficult for these adolescents already affected by an heavy chronic disease. The monitoring of the children should thus now become pluridisciplinary and include regular clinical evaluation of height and pubertal status, mineral bone density by DEXA and OGTT every two years since 10 years of age. Therefore, in addition to the standard treatment of cystic fibrosis is now added the vitamin D supplementation, the subcutaneous insulin therapy and may be the growth hormone that could be a new therapeutic demonstrating beneficial effects in these chronic disease. However further studies need to be performed to improve the management of these new endocrine complications more and more frequent in children and adolescents suffering from cystic fibrosis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  19. Low dose rate Ir-192 interstitial brachytherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oki, Yosuke; Dokiya, Takushi; Yorozu, Atsunori; Suzuki, Takayuki; Saito, Shiro; Monma, Tetsuo; Ohki, Takahiro [National Tokyo Medical Center (Japan); Murai, Masaru; Kubo, Atsushi

    2000-04-01

    From December 1997 through January 1999, fifteen prostatic cancer patients were treated with low dose rate Ir-192 interstitial brachytherapy using TRUS and perineal template guidance without external radiotherapy. Up to now, as no apparent side effects were found, the safety of this treatment is suggested. In the future, in order to treat prostatic cancer patients with interstitial brachytherapy using I-125 or Pd-103, more investigation for this low dose rate Ir-192 interstitial brachytherapy is needed. (author)

  20. 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

  1. Assessment and management of refractory breathlessness in interstitial lung disease.

    Science.gov (United States)

    Speakman, Lucy; Walthall, Helen

    2017-09-02

    Interstitial lung disease (ILD) refers to a cluster of fibroinflammatory conditions. There are limited treatment options and most patients have severe dyspnoea. The prognosis is poor. This study aims to evaluate current literature on the assessment and management of refractory breathlessness in ILD. Few tools are available to assess dyspnoea in advanced respiratory disease. Holistic assessment requires a combination of tools but there are few disease specific tools. The role of opioids is well established in the reduction of breathlessness, but there is insufficient evidence that benzodiazepines are beneficial. Non-pharmcolological breathlessness intervention services can give patients mastery of their disease, reduced distress due to breathlessness and were more cost effective. More research on holistic interventions for use in advanced disease needs to be done. Patient-reported outcome measures could elicit valuable evidence to describe the benefit of breathlessness management services in advanced respiratory disease.

  2. Renal extramedullary hematopoiesis: interstitial and glomerular pathology.

    Science.gov (United States)

    Alexander, Mariam P; Nasr, Samih H; Kurtin, Paul J; Casey, Edward T; Hernandez, Loren P Herrera; Fidler, Mary E; Sethi, Sanjeev; Cornell, Lynn D

    2015-12-01

    Renal extramedullary hematopoiesis is rarely recognized in the antemortem setting. We identified 14 patients with renal extramedullary hematopoiesis on antemortem specimens from 1994 to 2015. The mean age was 68 years (range 47-87 years); males predominated (M:F=9:5). All presented with renal insufficiency, including five (36%) with acute kidney injury. The mean serum creatinine at biopsy was 2.9 mg/dl (range 1.2-7.3 mg/dl). All had proteinuria (mean 7.9 g/24 h; range 0.5-28; n=13), including 9 with ≥3 g/24 h. Renal extramedullary hematopoiesis appeared histologically as an interstitial infiltrate (n=12) and/or a perirenal infiltrate (n=3) or mass-like lesion (n=1). Five were misdiagnosed as interstitial nephritis. Concurrent glomerular disease was prevalent and included fibrillary-like glomerulonephritis (n=3), chronic thrombotic microangiopathy (n=5), focal segmental glomerulosclerosis (n=6), and diabetic glomerulosclerosis (n=2). All patients had an underlying hematologic malignancy: primary myelofibrosis in 9, myeloproliferative neoplasm not otherwise specified in 1, essential thrombocythemia in 1, polycythemia vera in 1, and plasma cell myeloma in 2. Clinical follow-up was available in 12 patients, mean of 29 months (range 4-120 months). In 10 patients for whom treatment history could be obtained, 9 were treated with chemotherapy, and 1 was treated with steroids. The mean creatinine at last follow-up was 2 mg/dl (range 1.2-3.9 mg/dl) (n=9). Ten patients died in the follow-up period from their underlying hematological disease and had persistent renal disease. The two remaining patients had persistent chronic kidney disease. Renal extramedullary hematopoiesis should be considered in the differential diagnosis of interstitial infiltrates, particularly in the presence of a glomerulopathy and a hematologic malignancy.

  3. Sapphire capillary interstitial irradiators for laser medicine

    Science.gov (United States)

    Shikunova, I. A.; Dolganova, I. N.; Dubyanskaya, E. N.; Mukhina, E. E.; Zaytsev, K. I.; Kurlov, V. N.

    2018-04-01

    In this paper, we demonstrate instruments for laser radiation delivery based on sapphire capillary needles. Such sapphire irradiators (introducers) can be used for various medical applications, such as photodynamic therapy, laser hyperthermia, laser interstitial thermal therapy, and ablation of tumors of various organs. Unique properties of sapphire allow for effective redistribution of the heat, generated in biological tissues during their exposure to laser radiation. This leads to homogeneous distribution of the laser irradiation around the needle, and lower possibility of formation of the overheating focuses, as well as the following non-transparent thrombi.

  4. Lung volumes and emphysema in smokers with interstitial lung abnormalities.

    Science.gov (United States)

    Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

    2011-03-10

    Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; Ppulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

  5. Migration of di- and tri-interstitials in silicon

    International Nuclear Information System (INIS)

    Posselt, M.; Gao, F.; Zwicker, D.

    2005-01-01

    A comprehensive study on the migration of di- and tri-interstitials in silicon is performed using classical molecular dynamics simulations with the Stillinger-Weber potential. The initial di- and tri-interstitial configurations with the lowest formation energies are determined, and then, the defect migration is investigated for temperatures between 800 and 1600 K. The defect diffusivity and the self-diffusion coefficient per defect are calculated. Compared to the mono-interstitial, the di-interstitial migrates faster, whereas the tri-interstitial diffuses slower. The migration mechanism of the di-interstitial shows a pronounced dependence on the temperature. Like in the case of the mono-interstitial, the mobility of the di-interstitial is higher than the mobility of the lattice atoms during the defect diffusion. On the other hand, the tri-interstitial mobility is lower than the corresponding atomic mobility. The implications of the present results for the analysis of experimental data on defect evolution and migration are discussed

  6. 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.

  7. Radiotherapy and pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Sone, S; Miyata, Y; Tachiiri, H [Osaka Univ. (Japan). Faculty of Medicine

    1975-04-01

    Clinical findings of radiation pneumonitis and pulmonary fibrosis were outlined, and the relationship between occurence of these disorders and radiotherapy, clinical findings and X-ray picture were studied. Standard radiation dose as cell lethal response of carcinoma of the lung were 4,500 to 5,500 rad in 4 to 5.5 weeks in undifferentiated carcinoma, 6,000 to 7,000 rad in 6 to 7 weeks in squamous cell carcinoma, 7,000 to 9,000 rad in 7 to 9 weeks in adenocarcinoma, 4,500 to 5,000 rad in 4 to 5 weeks in the large sized cancer of the esophagus, 6,500 to 7,000 rad in 5 to 7 weeks in the small sized cancer of the esophagus, and irradiation of these amount of dose caused hazards in pulmonary function. Pathological and clinical findings of pulmonary hazards within 6 month period after irradiation, factors causing them and changes in X-ray pictures before and after irradiation were observed and discussed in clinical cases: the case of breast cancer in which 3,000 R/6 times/18 days of 5.5 MeV Liniac electron was irradiated to the chest wall, and the case of pulmonary cancer in which 5,000 rad/25 times/34 days of 6 MeV Liniac X-ray was irradiated in opposite 2 ports radiation beam treatment. The former revealed alveolar lesion and interlobular pleuritis at 4 month later, and remarkable lesion of pulmonary fibrosis was followed at 9 month after radiotherapy. The later developed radiation pneumonitis 1 month after radiotherapy, of which lesion extended to the upper part by 3 months later, and cancer recurred 6.5 month later.

  8. Interstitial hydraulic conductivity and interstitial fluid pressure for avascular or poorly vascularized tumors.

    Science.gov (United States)

    Liu, L J; Schlesinger, M

    2015-09-07

    A correct description of the hydraulic conductivity is essential for determining the actual tumor interstitial fluid pressure (TIFP) distribution. Traditionally, it has been assumed that the hydraulic conductivities both in a tumor and normal tissue are constant, and that a tumor has a much larger interstitial hydraulic conductivity than normal tissue. The abrupt transition of the hydraulic conductivity at the tumor surface leads to non-physical results (the hydraulic conductivity and the slope of the TIFP are not continuous at tumor surface). For the sake of simplicity and the need to represent reality, we focus our analysis on avascular or poorly vascularized tumors, which have a necrosis that is mostly in the center and vascularization that is mostly on the periphery. We suggest that there is an intermediary region between the tumor surface and normal tissue. Through this region, the interstitium (including the structure and composition of solid components and interstitial fluid) transitions from tumor to normal tissue. This process also causes the hydraulic conductivity to do the same. We introduce a continuous variation of the hydraulic conductivity, and show that the interstitial hydraulic conductivity in the intermediary region should be monotonically increasing up to the value of hydraulic conductivity in the normal tissue in order for the model to correspond to the actual TIFP distribution. The value of the hydraulic conductivity at the tumor surface should be the lowest in value. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. IgG4-related lung disease presenting as interstitial lung disease with bronchiolitis: A case report.

    Science.gov (United States)

    Chen, Chiu-Fan; Chu, Kuo-An; Tseng, Yen-Chiang; Wu, Chang-Che; Lai, Ruay-Sheng

    2017-12-01

    IgG4-related disease is a rare and novel disease entity that tends to involve multiple organs. The pulmonary manifestation of this disease is highly variable and may mimic lung cancer, pneumonia, interstitial lung disease (ILD), sarcoidosis, and so forth. Small airway disease is rarely reported in IgG4-related lung disease (IgG4-RLD). In the current study, we describe a rare case of IgG4-RLD with patterns of ILD and bronchiolitis. A 43-year-old man had chronic cough and dyspnea on exertion for 4 years. Initial chest radiography showed diffuse interstitial infiltration. Follow-up chest computed tomography 4 years later revealed bilateral diffuse centrilobular nodules with tree-in-bud pattern, bronchial wall thickening, and mediastinal lymph nodes. Bilateral diffuse multifocal ground-glass opacities and mosaic attenuation were also observed. Pulmonary function test revealed mixed restrictive and obstructive ventilatory impairment. Video-assisted thoracoscopic surgery (VATS) lung biopsy showed interstitial fibrosis with lymphoplasmacytic infiltration rich in IgG4-positive plasma cells. Serum IgG4 level also showed remarkable elevation. Therefore, IgG4-RLD is confirmed. VATS wedge resection of right upper lobe and mediastinal lymph node. The patient responded well to steroid and immunosuppression therapy, and was regular followed-up in outpatient clinic. IgG4-RLD should be considered not only in ILD, but also in small airway disease. Serum IgG4 level may be a useful tool for screening.

  10. Doença pulmonar intersticial associada a bronquiolite respiratória Respiratory bronchilitis-associated interstitial lung disease

    Directory of Open Access Journals (Sweden)

    Sílvia CS. Rodrigues

    2004-12-01

    Full Text Available A doença pulmonar intersticial associada a bronquiolite respiratória faz parte do espectro anatomopatológico das lesões pulmonares infiltrativas difusas induzidas pela fumaça de cigarro. Raramente tem apresentação clínico-funcional exuberante. Descrevemos dois casos diagnosticados por biópsia pulmonar aberta, caracterizados por dispnéia de evolução insidiosa, baqueteamento digital, lesões císticas à tomografia computadorizada e hipoxemia ao exercício. Enfatizamos considerar, em indivíduos tabagistas, a doença pulmonar intersticial associada a bronquiolite respiratória no contexto das pneumopatias intersticiais císticas, juntamente com a linfangioleiomiomatose, o granuloma eosinofílico e a fibrose pulmonar idiopática.Respiratory bronchiolitis-associated interstitial lung disease is one of many within the spectrum of smoking-related diffuse infiltrative lung diseases. The clinical and functional characteristics are typically subtle. Herein, we describe two cases of diagnosed through open-lung biopsy, and characterized by insidious evolution of dyspnea, digital clubbing, cystic lesions on computed tomography scans, and hipoxemia upon exertion. We emphasize that, when smokers are evaluated, it is imprtant to consider a diagnosis of respiratory bronchiolitis-associated interstitial lung disease in the context of interstitial cystitis, as well as in that of lymphangioleiomyomatosis, eosinophilic granuloma and idiophatic pulmonary fibrosis.

  11. Formation and annealing of metastable (interstitial oxygen)-(interstitial carbon) complexes in n- and p-type silicon

    CERN Document Server

    Makarenko, L F; Lastovskii, S B; Murin, L I; Moll, M; Pintilie, I

    2014-01-01

    It is shown experimentally that, in contrast to the stable configuration of (interstitial carbon)-(interstitial oxygen) complexes (CiOi), the corresponding metastable configuration (CiOi{*}) cannot be found in n-Si based structures by the method of capacitance spectroscopy. The rates of transformation CiOi{*} -> CiOi are practically the same for both n- and p-Si with a concentration of charge carriers of no higher than 10(13) cm(-3). It is established that the probabilities of the simultaneous formation of stable and metastable configurations of the complex under study in the case of the addition of an atom of interstitial carbon to an atom of interstitial oxygen is close to 50\\%. This is caused by the orientation dependence of the interaction potential of an atom of interstitial oxygen with an interstitial carbon atom, which diffuses to this oxygen atom.

  12. Heterogeneity in Fibroblast Proliferation and Survival in Idiopathic Pulmonary Fibrosis

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    David Michael Habiel

    2014-01-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. Myofibroblasts have been shown to arise from interstitial fibroblasts, epithelial to mesenchymal transition of type II alveolar epithelial cells, and the differentiation of recruited fibrocytes. There are many mechanisms that are utilized by these cells for survival, proliferation and persistent activation including up-regulation of cytokines (i.e. Interlukin 6 (IL-6, cytokine receptors (i.e. Interlukin 6 Receptor 1 (IL-6R1, Glycoprotein 130 (gp130 and C-C Chemokine Receptor type 7 (CCR7 and innate pattern recognition receptors (PRRs; i.e. Toll Like Receptor 9 (TLR9. In this review, we will discuss the role of the cytokines IL-6 and CCL21, their receptors and the pattern recognition receptor (PRR, TLR9, in fibroblast recruitment, activation, survival and differentiation into myofibroblasts in IPF.

  13. Combined pulmonary fibrosis and emphysema: an increasingly recognized condition

    Directory of Open Access Journals (Sweden)

    Olívia Meira Dias

    2014-06-01

    Full Text Available Combined pulmonary fibrosis and emphysema (CPFE has been increasingly recognized in the literature. Patients with CPFE are usually heavy smokers or former smokers with concomitant lower lobe fibrosis and upper lobe emphysema on chest HRCT scans. They commonly present with severe breathlessness and low DLCO, despite spirometry showing relatively preserved lung volumes. Moderate to severe pulmonary arterial hypertension is common in such patients, who are also at an increased risk of developing lung cancer. Unfortunately, there is currently no effective treatment for CPFE. In this review, we discuss the current knowledge of the pathogenesis, clinical characteristics, and prognostic factors of CPFE. Given that most of the published data on CPFE are based on retrospective analysis, more studies are needed in order to address the role of emphysema and its subtypes; the progression of fibrosis/emphysema and its correlation with inflammation; treatment options; and prognosis.

  14. Understanding the Process of Fibrosis in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Yacine Kharraz

    2014-01-01

    Full Text Available Fibrosis is the aberrant deposition of extracellular matrix (ECM components during tissue healing leading to loss of its architecture and function. Fibrotic diseases are often associated with chronic pathologies and occur in a large variety of vital organs and tissues, including skeletal muscle. In human muscle, fibrosis is most readily associated with the severe muscle wasting disorder Duchenne muscular dystrophy (DMD, caused by loss of dystrophin gene function. In DMD, skeletal muscle degenerates and is infiltrated by inflammatory cells and the functions of the muscle stem cells (satellite cells become impeded and fibrogenic cells hyperproliferate and are overactivated, leading to the substitution of skeletal muscle with nonfunctional fibrotic tissue. Here, we review new developments in our understanding of the mechanisms leading to fibrosis in DMD and several recent advances towards reverting it, as potential treatments to attenuate disease progression.

  15. Diagnosis of different liver fibrosis characteristics by blood tests in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Calès, Paul; Boursier, Jérôme; Chaigneau, Julien; Lainé, Fabrice; Sandrini, Jeremy; Michalak, Sophie; Hubert, Isabelle; Dib, Nina; Oberti, Frédéric; Bertrais, Sandrine; Hunault, Gilles; Cavaro-Ménard, Christine; Gallois, Yves; Deugnier, Yves; Rousselet, Marie C

    2010-10-01

    Our aim was to develop an accurate, non-invasive, blood-test-based method for identifying the main characteristics of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Fibrosis was staged according to NASH-CRN and Metavir systems in 226 patients with NAFLD. A fully automated algorithm measured the fractal dimension (FD) and the area of fibrosis (AOF). Independent predictors of diagnostic targets were determined using bootstrap methods. (i) Development. Significant fibrosis defined by NASH-CRN F ≥2 was diagnosed by weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and prothrombin index [area under the receiver operating characteristic (AUROC)=0.867]; significant fibrosis defined by Metavir F ≥2 was diagnosed by weight, age, glycaemia, AST, ALT, ferritin and platelets (FibroMeter AUROC=0.941, Pfibrosis staging, Metavir staging was a better reference for blood test. Thus, the patient rate with predictive values ≥90% by tests was 97.3% with Metavir reference vs. 66.5% with NASH-CRN reference (Pfibrosis score for significant fibrosis, but not for severe fibrosis or cirrhosis, with both staging systems. Relationships between fibrosis lesions were well reflected by blood tests, e.g., the correlation between histological area and FD of fibrosis (r(s) =0.971, Pblood tests (r(s) =0.852, Pfibrosis in NAFLD can be diagnosed and quantified by blood tests with excellent accuracy. © 2010 John Wiley & Sons A/S.

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

    Science.gov (United States)

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

    2009-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Bastiaan J van Nierop

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

  18. First-principles studies of di-arsenic interstitial and its implications for arsenic-interstitial diffusion in crystalline silicon

    International Nuclear Information System (INIS)

    Kim, Yonghyun; Kirichenko, Taras A.; Kong, Ning; Larson, Larry; Banerjee, Sanjay K.

    2007-01-01

    We propose new structural configurations and novel diffusion mechanisms for neutral di-arsenic interstitial (As 2 I 2 ) in silicon with a first-principle density functional theory simulation within the generalized gradient approximation. With an assumption of excess silicon interstitials and high arsenic concentrations, neutral As 2 I 2 is expected to be favorable and mobile with low-migration barrier. Moreover, because the diffusion barrier of arsenic interstitial pairs (AsI) is very low ( 2 I 2 can be easily formed and likely intermediate stage of larger arsenic interstitial clusters

  19. Energetics of formation and migration of self-interstitials and self-interstitial clusters in α-iron

    International Nuclear Information System (INIS)

    Wirth, B.D.; Odette, G.R.; California Univ., Santa Barbara, CA; Maroudas, D.; Lucas, G.E.; California Univ., Santa Barbara, CA

    1997-01-01

    Energetic primary recoil atoms from fast neutron irradiation generate both isolated point defects and clusters of vacancies and interstitials. Self-interstitial mobility as well as defect cluster stability and mobility play key roles in the subsequent fate of defects and, hence, in the overall microstructural evolution under irradiation. Self-interstitials and two, three and four-member self-interstitial clusters are highly mobile at low temperatures as observed in molecular-dynamics simulations and high mobility probably also extends to larger clusters. In this study, the morphology, energetics and mobility of self-interstitials and small self-interstitial clusters in α-iron are studied by molecular-statics and molecular-dynamics simulations using a Finnis-Sinclair many-body interatomic potential. Self-interstitial migration is found to be a two-step process consisting of a rotation out of the split-dumbbell configuration into the split-dumbbell configuration and translational jumps through the crowdion configuration before returning to the dumbbell configuration. Self-interstitial clusters of type split-interstitials assembled on adjacent {110} planes migrate along directions in an amoeba-like fashion by sequential local dissociation and re-association processes. (orig.)

  20. The Interstitial Language and Transnational Experience

    Directory of Open Access Journals (Sweden)

    Paolo Bartoloni

    2013-08-01

    Full Text Available In this essay I argue that the idea of inhabiting, and of human individuality as the house of being, are fruitful ideas if located in a space defined by movement, porosity, interstitiality, and in an urban and architectural paradigm which is based on openness and inclusiveness. Transnational experiences and localities can be, to this end, extremely instructive. It is essential to articulate the notion of dwelling within an urban context in which building is the result of complex cultural and social interactions, which are characterised not only by the negotiation of space and materials but also, and more importantly, by a range of symbolic values. The symbolism that I refer to here is the product of mnemonic and emotional experiences marked by time and space, which in the case of the migratory and transnational experiences is arrived at through a delicate negotiation of the past and the present, and the ‘here’ (the current locality and the ‘there’ (the native locality. The dwelling that I speak of is, therefore, a double dwelling divided between the present at-hand and the remembered past, and as such it inhabits a space, which is both interstitial and liminal, simultaneously in and out-of-place. I have chosen the Italian Forum in Sydney as a working sample of the place-out-of-place

  1. Interstitial Fe in MgO

    CERN Document Server

    Mølholt, T E; Gunnlaugsson, H P; Svane, A; Masenda, H; Naidoo, D; Bharuth-Ram, K; Fanciulli, M; Gislason, H P; Johnston, K; Langouche, G; Ólafsson, S; Sielemann, R; Weyer, G

    2014-01-01

    Isolated Fe-57 atoms were studied in MgO single-crystals by emission Mossbauer spectroscopy following implantation of Mn-57 decaying to Fe-57. Four Mossbauer spectral components were found corresponding to different Fe lattice positions and/or charge states. Two components represent Fe atoms substituting Mg as Fe2+ and Fe3+, respectively; a third component is due to Fe in a strongly implantation-induced disturbed region. The fourth component, which is the focus of this paper, can be assigned to Fe at an interstitial site. Comparison of its measured isomer shift with ab initio calculations suggests that the interstitial Fe is located on, or close to, the face of the rock-salt MgO structure. To harmonize such an assignment with the measured near-zero quadrupole interaction a local motion process (cage motion) of the Fe has to be stipulated. The relation of such a local motion as a starting point for long range diffusion is discussed.

  2. Pneumothorax and idiopathic pulmonary fibrosis

    International Nuclear Information System (INIS)

    Iwasawa, Tae; Ogura, Takashi; Takahashi, Hiroshi; Asakura, Akira; Gotoh, Toshiyuki; Yazawa, Takuya; Inoue, Tomio

    2010-01-01

    We evaluated the relation between the severity of idiopathic pulmonary fibrosis (IPF) and the incidence of pneumothorax on computed tomography (CT) images. In this retrospective study, we evaluated the presence of pneumothorax in 56 consecutive patients who died of IPF from the initial CT to death. We quantitatively analyzed a total of 207 CT images and measured the volume of the normal pattern (N-pattern) and each lesion pattern on the initial CT and their serial changes. The effects of pneumothorax and clinical and CT features on survival were evaluated using Cox regression analysis. Pneumothorax occurred in 17 of 56 patients. Comparison of the pneumothorax (+) and (-) groups showed the initial vital capacity (VC) was lower (P=0.005) and the follow-up period was shorter (P=0.03) in the former group. The decrease in the N-pattern volume in the pneumothorax (+) group was significantly faster than in the pneumothorax (-) group (P=0.013). Cox regression analyses identified a rapid decrease in N-pattern volume (P=0.008) and a rapid decrease in VC (P=0.002), but not pneumothorax, as significant predictors of poor survival. Pneumothorax in IPF patients is associated with lower VC and rapid deterioration of CT findings. The findings suggest that pneumothorax is a complication of advanced IPF. (author)

  3. Differential gene expression in the murine gastric fundus lacking interstitial cells of Cajal

    Directory of Open Access Journals (Sweden)

    Ward Sean M

    2003-06-01

    Full Text Available Abstract Background The muscle layers of murine gastric fundus have no interstitial cells of Cajal at the level of the myenteric plexus and only possess intramuscular interstitial cells and this tissue does not generate electric slow waves. The absence of intramuscular interstitial cells in W/WV mutants provides a unique opportunity to study the molecular changes that are associated with the loss of these intercalating cells. Method The gene expression profile of the gastric fundus of wild type and W/WV mice was assayed by murine microarray analysis displaying a total of 8734 elements. Queried genes from the microarray analysis were confirmed by semi-quantitative reverse transcription-polymerase chain reaction. Results Twenty-one genes were differentially expressed in wild type and W/WV mice. Eleven transcripts had 2.0–2.5 fold higher mRNA expression in W/WV gastric fundus when compared to wild type tissues. Ten transcripts had 2.1–3.9 fold lower expression in W/WV mutants in comparison with wild type animals. None of these genes have ever been implicated in any bowel motility function. Conclusions These data provides evidence that several important genes have significantly changed in the murine fundus of W/WV mutants that lack intramuscular interstitial cells of Cajal and have reduced enteric motor neurotransmission.

  4. Therapeutic targets in liver fibrosis.

    Science.gov (United States)

    Fallowfield, Jonathan A

    2011-05-01

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

  5. Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy

    Science.gov (United States)

    2014-01-01

    Background Fibrosis, an excessive collagen accumulation, results in scar formation, impairing function of vital organs and tissues. Fibrosis is a hallmark of muscular dystrophies, including the lethal Duchenne muscular dystrophy (DMD), which remains incurable. Substitution of muscle by fibrotic tissue also complicates gene/cell therapies for DMD. Yet, no optimal models to study muscle fibrosis are available. In the widely used mdx mouse model for DMD, extensive fibrosis develops in the diaphragm only at advanced adulthood, and at about two years of age in the ‘easy-to-access’ limb muscles, thus precluding fibrosis research and the testing of novel therapies. Methods We developed distinct experimental strategies, ranging from chronic exercise to increasing muscle damage on limb muscles of young mdx mice, by myotoxin injection, surgically induced trauma (laceration or denervation) or intramuscular delivery of profibrotic growth factors (such as TGFβ). We also extended these approaches to muscle of normal non-dystrophic mice. Results These strategies resulted in advanced and enhanced muscle fibrosis in young mdx mice, which persisted over time, and correlated with reduced muscle force, thus mimicking the severe DMD phenotype. Furthermore, increased fibrosis was also obtained by combining these procedures in muscles of normal mice, mirroring aberrant repair after severe trauma. Conclusions We have developed new and improved experimental strategies to accelerate and enhance muscle fibrosis in vivo. These strategies will allow rapidly assessing fibrosis in the easily accessible limb muscles of young mdx mice, without necessarily having to use old animals. The extension of these fibrogenic regimes to the muscle of non-dystrophic wild-type mice will allow fibrosis assessment in a wide array of pre-existing transgenic mouse lines, which in turn will facilitate understanding the mechanisms of fibrogenesis. These strategies should improve our ability to combat fibrosis

  6. Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, Mark M.; Sheybani, Elizabeth F. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway Blvd., Campus Box 8131, St. Louis, MO (United States); Zhang, Lingxin [Washington University School of Medicine, Department of Pathology, St. Louis, MO (United States); Stoll, Janis M. [Washington University School of Medicine, Division of Gastroenterology, Hepatology and Nutrition, St. Louis, MO (United States)

    2016-04-15

    We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. (orig.)

  7. Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation

    International Nuclear Information System (INIS)

    Hammer, Mark M.; Sheybani, Elizabeth F.; Zhang, Lingxin; Stoll, Janis M.

    2016-01-01

    We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. (orig.)

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

    Directory of Open Access Journals (Sweden)

    J.J. Egan

    2011-06-01

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

  9. Erectile dysfunction is a common problem in interstitial lung diseases

    DEFF Research Database (Denmark)

    Fløe, Andreas; Hilberg, Ole; Wijsenbeek, Marlies

    2017-01-01

    Introduction: Erectile dysfunction (ED) is related to chronic diseases, including COPD. The patho- genesis may involve chronic hypoxia, which is common in interstitial lung disease (ILD). We aimed to study the relationship between ILD and ED. Method: Male patients with ILD detected by high...... degree of ED, thirty (56.6%) had moderate to severe ED, and 23 (43.4%) had severe ED. Low diffusion capacity and high body mass index showed a trend of increasing risk of moderate to severe ED. The risk increased with age (OR per 5-year increase=2.63 (1.25; 5.53)) and decreased with 6MWT distance (OR per...... 50 m increase=0.60 (0.41; 0.89). Only two patients (6.7%) received specific treatment with phosphodiesterase-5 inhibitors. Conclusion: Severe ED is a common