Effects of Angiotensin Converting Enzyme Inhibitors on Liver Fibrosis in HIV and Hepatitis C Coinfection

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Lindsey J. Reese

2012-01-01

Full Text Available Background. Liver fibrosis is accelerated in HIV and hepatitis C coinfection, mediated by profibrotic effects of angiotensin. The objective of this study was to determine if angiotensin converting enzyme inhibitors (ACE-Is attenuate liver fibrosis in coinfection. Methods. A retrospective review of 156 coinfected subjects was conducted to analyze the association between exposure to ACE-Is and liver fibrosis. Noninvasive indices of liver fibrosis (APRI, FIB-4, Forns indices were compared between subjects who had taken ACE-Is and controls who had not taken them. Linear regression was used to evaluate ACE-I use as an independent predictor of fibrosis. Results. Subjects taking ACE-Is for three years were no different than controls on the APRI and the FIB-4 but had significantly higher scores than controls on the Forns index, indicating more advanced fibrosis. The use of ACE-Is for three years remained independently associated with an elevated Forns score when adjusted for age, race, and HIV viral load (P<0.001. There were significant associations between all of the indices and significant fibrosis, as determined clinically and radiologically. Conclusions. There was not a protective association between angiotensin inhibition and liver fibrosis in coinfection. These noninvasive indices may be useful for ruling out significant fibrosis in coinfection.

Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

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Mora, Ana L.; Rojas, Mauricio

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a chronic age-related lung disease with high mortality that is characterized by abnormal scarring of the lung parenchyma. There has been a recent attempt to define the age-associated changes predisposing individuals to develop IPF. Age-related perturbations that are increasingly found in epithelial cells and fibroblasts from IPF lungs compared with age-matched cells from normal lungs include defective autophagy, telomere attrition, altered proteostasis, and cell senescence. These divergent processes seem to converge in mitochondrial dysfunction and metabolic distress, which potentiate maladaptation to stress and susceptibility to age-related diseases such as IPF. Therapeutic approaches that target aging processes may be beneficial for halting the progression of disease and improving quality of life in IPF patients. PMID:28145905

Self-reported exercise and longitudinal outcomes in cystic fibrosis: a retrospective cohort study.

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Collaco, Joseph M; Blackman, Scott M; Raraigh, Karen S; Morrow, Christopher B; Cutting, Garry R; Paranjape, Shruti M

2014-10-06

Cystic fibrosis (CF) is characterized by recurrent respiratory infections and progressive lung disease. Whereas exercise may contribute to preserving lung function, its benefit is difficult to ascertain given the selection bias of healthier patients being more predisposed to exercise. Our objective was to examine the role of self-reported exercise with longitudinal lung function and body mass index (BMI) measures in CF. A total of 1038 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine exercise habits. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track outcomes. Within the study sample 75% of subjects self-reported regular exercise. Exercise was associated with an older age of diagnosis (p = 0.002), older age at the time of ascertainment (p nutritional and pulmonary outcomes in cystic fibrosis for adults. Although prospective studies are needed to confirm these associations, programs to promote regular exercise among individuals with cystic fibrosis would be beneficial.

Endomyocardial fibrosis in infancy

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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.

NUTRITIONAL STATUS IS ASSOCIATED WITH HEALTH-RELATED QUALITY OF LIFE IN CHILDREN WITH CYSTIC FIBROSIS AGED 9–19 YEARS

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Shoff, Suzanne M.; Tluczek, Audrey; Laxova, Anita; Farrell, Philip M.; Lai, HuiChuan J.

2013-01-01

Background The impact of improved nutritional status on health-related quality of life (HRQOL) is unknown for children with cystic fibrosis (CF). Methods Associations between nutritional status and HRQOL were examined over 2 years in 95 children, aged 9–19 years, who were followed in the Wisconsin Newborn Screening Project. HRQOL was assessed using the Cystic Fibrosis Questionnaire (CFQ). Associations between height z-score (HtZ), BMI z-score (BMIZ) and seven CFQ dimensions were evaluated. Results Mean values of at least 80 were observed for all CFQ dimensions except respiratory symptoms and treatment burden. Treatment burden was significantly worse in patients with meconium ileus (57) compared to pancreatic insufficient (65) and sufficient (78) subjects, pnutritional status was associated with increased HRQOL scores. Early diagnosis through newborn screening and improved nutrition provides an opportunity to enhance quality of life and body image perception. PMID:23410621

Case-control study of gadodiamide-related nephrogenic systemic fibrosis

DEFF Research Database (Denmark)

Marckmann, Peter; Skov, Lone; Rossen, Kristian

2007-01-01

exposed to gadodiamide develop nephrogenic systemic fibrosis. METHODS: We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to gadodiamide. Clinical, biochemical and pharmacological data were.......02). CONCLUSIONS: Increasing cumulative gadodiamide exposure, high-dose epoietin-beta treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients......BACKGROUND: Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients...

Cytochemical localization of small intestinal glycoconjugates by lectin histochemistry in controls and subjects with cystic fibrosis.

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Jacobs, L R; De Fontes, D; Cox, K L

1983-05-01

Human mucosal glycoconjugates were examined in normal small intestinal biopsies from five control subjects using six different fluorescein-conjugated lectins: Triticum vulgare agglutinin (WGA), Ulex europaeus agglutinin I (UEA1), Ricinus communis agglutinin I (RCA1), glycin max-soy bean agglutinin (SBA), Dolichus biflorus agglutinin (DBA), and Arachis hypogaea peanut agglutinin (PNA). These plant agglutinins bind to specific nonreducing end-terminal carbohydrate residues. Only the lectins derived from WGA, which produced the strongest staining, and UEA1 consistently bound to both intestinal goblet cell mucin and epithelial cell microvillar membranes. The intensity of lectin binding was greatest in the upper villus and diminished down towards the crypt, being weakest in the crypt base. Similar histochemical studies carried out on small bowel biopsies from five patients with cystic fibrosis revealed no major qualitative differences between the intestinal glycoconjugates in normal subjects and those with cystic fibrosis. These results suggest that glycoconjugate biosynthesis of human intestinal goblet cell mucin and epithelial cell membranes may be complete and hence full differentiation achieved only when these cells have migrated out of the crypt and onto the villus.

Voice Disorder in Cystic Fibrosis Patients

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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

Prediction of fibrosis progression in chronic viral hepatitis

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Grace Lai-Hung Wong

2014-09-01

Full Text Available Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

Myocardial fibrosis burden predicts left ventricular ejection fraction and is associated with age and steroid treatment duration in duchenne muscular dystrophy.

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Tandon, Animesh; Villa, Chet R; Hor, Kan N; Jefferies, John L; Gao, Zhiqian; Towbin, Jeffrey A; Wong, Brenda L; Mazur, Wojciech; Fleck, Robert J; Sticka, Joshua J; Benson, D Woodrow; Taylor, Michael D

2015-03-26

Patients with Duchenne muscular dystrophy exhibit progressive cardiac and skeletal muscle dysfunction. Based on prior data, cardiac dysfunction in Duchenne muscular dystrophy patients may be influenced by myocardial fibrosis and steroid therapy. We examined the longitudinal relationship of myocardial fibrosis and ventricular dysfunction using cardiac magnetic resonance in a large Duchenne muscular dystrophy cohort. We reviewed 465 serial cardiac magnetic resonance studies (98 Duchenne muscular dystrophy patients with ≥4 cardiac magnetic resonance studies) for left ventricular ejection fraction (LVEF) and presence of late gadolinium enhancement (LGE), a marker for myocardial fibrosis. LVEF was modeled by examining LGE status, myocardial fibrosis burden (as assessed by the number of LGE-positive left ventricular segments), patient age, and steroid treatment duration. An age-only model demonstrated that LVEF declined 0.58 ± 0.10% per year. In patients with both LGE-negative and LGE-positive studies (n=51), LVEF did not decline significantly over time if LGE was absent but declined 2.2 ± 0.31% per year when LGE was present. Univariate modeling showed significant associations between LVEF and steroid treatment duration, presence of LGE, and number of LGE-positive left ventricular segments; multivariate modeling showed that LVEF declined by 0.93 ± 0.09% for each LGE-positive left ventricular segment, whereas age and steroid treatment duration were not significant. The number of LGE-positive left ventricular segments increased with age, and longer steroid treatment duration was associated with lower age-related increases. Progressive myocardial fibrosis, as detected by LGE, was strongly correlated with the LVEF decline in Duchenne muscular dystrophy patients. Longer steroid treatment duration was associated with a lower age-related increase in myocardial fibrosis burden. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley

Fibrosis-Related Gene Expression in Single Ventricle Heart Disease.

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Nakano, Stephanie J; Siomos, Austine K; Garcia, Anastacia M; Nguyen, Hieu; SooHoo, Megan; Galambos, Csaba; Nunley, Karin; Stauffer, Brian L; Sucharov, Carmen C; Miyamoto, Shelley D

2017-12-01

To evaluate fibrosis and fibrosis-related gene expression in the myocardium of pediatric subjects with single ventricle with right ventricular failure. Real-time quantitative polymerase chain reaction was performed on explanted right ventricular myocardium of pediatric subjects with single ventricle disease and controls with nonfailing heart disease. Subjects were divided into 3 groups: single ventricle failing (right ventricular failure before or after stage I palliation), single ventricle nonfailing (infants listed for primary transplantation with normal right ventricular function), and stage III (Fontan or right ventricular failure after stage III). To evaluate subjects of similar age and right ventricular volume loading, single ventricle disease with failure was compared with single ventricle without failure and stage III was compared with nonfailing right ventricular disease. Histologic fibrosis was assessed in all hearts. Mann-Whitney tests were performed to identify differences in gene expression. Collagen (Col1α, Col3) expression is decreased in single ventricle congenital heart disease with failure compared with nonfailing single ventricle congenital heart disease (P = .019 and P = .035, respectively), and is equivalent in stage III compared with nonfailing right ventricular heart disease. Tissue inhibitors of metalloproteinase (TIMP-1, TIMP-3, and TIMP-4) are downregulated in stage III compared with nonfailing right ventricular heart disease (P = .0047, P = .013 and P = .013, respectively). Matrix metalloproteinases (MMP-2, MMP-9) are similar between nonfailing single ventricular heart disease and failing single ventricular heart disease, and between stage III heart disease and nonfailing right ventricular heart disease. There is no difference in the prevalence of right ventricular fibrosis by histology in subjects with single ventricular failure heart disease with right ventricular failure (18%) compared with those with normal right

Aerosol scintigraphy in the assessment of therapy for cystic fibrosis

International Nuclear Information System (INIS)

Kuni, C.C.; Regelmann, W.E.; Budd, J.R.; Cret, R.P. du; Boudreau, R.J.

1990-01-01

This paper evaluates respiration therapy, counselling, and antibiotic therapy in the treatment of exacerbations of cystic fibrosis. Thirteen patients with cystic fibrosis, aged 11-32 years, who were hospitalized for exacerbation and who had sputum cultures positive for Pseudomonas were treated initially for 3 days with respiration therapy and counselling followed by 14 days of therapy with antibiotics (n = 7) or placebo (n = 6). Tc-99m-DTPA aerosol scintigraphy was performed on days, 1, 4, and 17. Scintigrams were evaluated for change in number of nonventilated segments, change in number of bronchial deposits of aerosol, and subjective overall change

Body composition of adult cystic fibrosis patients and control subjects as determined by densitometry, bioelectrical impedance, total-body electrical conductivity, skinfold measurements, and deuterium oxide dilution

International Nuclear Information System (INIS)

Newby, M.J.; Keim, N.L.; Brown, D.L.

1990-01-01

This study contrasts body compositions (by six methods) of eight cystic fibrosis (CF) subjects with those of eight control subjects matched for age, height, and sex. CF subjects weighed 84% as much as control subjects. Densitometry and two bioelectrical impedance-analysis methods suggested that reduced CF weights were due to less lean tissue (10.7, 9.5, and 10.4 kg). Total-body electrical conductivity (TOBEC) and skinfold-thickness measurements indicated that CF subjects were leaner than control subjects and had less fat (5.4 and 3.6 kg) and less lean (5.2 and 7 kg) tissue. D2O dilution showed a pattern similar to TOBEC (8.3 kg less lean, 2.7 kg less fat tissue). Densitometry estimates of fat (mass and percent) were not correlated (r less than 0.74, p greater than 0.05) with any other method for CF subjects but were correlated with all other methods for control subjects. CF subjects contained less fat and lean tissue than did control subjects. Densitometry by underwater weighing is unsuitable for assessing body composition of CF patients

Impact of liver fibrosis and fatty liver on T1rho measurements: A prospective study

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Xie, Shuang Shuang; Li, Qing; Cheng, Yue; Shen, Wen [Dept. of Radiology, Tianjin First Center Hospital, Tianjin (China); Zhang, Yu; Zhuo, Zhi Zheng [Clinical Science, Philips Healthcare, Beijing (China); Zhao, Guiming [Dept. of Hepatology, Tianjin Second People' s Hospital, Tianjin (China)

2017-11-15

To investigate the liver T1rho values for detecting fibrosis, and the potential impact of fatty liver on T1rho measurements. This study included 18 healthy subjects, 18 patients with fatty liver, and 18 patients with liver fibrosis, who underwent T1rho MRI and mDIXON collections. Liver T1rho, proton density fat fraction (PDFF) and T2* values were measured and compared among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the T1rho values for detecting liver fibrosis. Liver T1rho values were correlated with PDFF, T2* values and clinical data. Liver T1rho and PDFF values were significantly different (p < 0.001), whereas the T2* (p = 0.766) values were similar, among the three groups. Mean liver T1rho values in the fibrotic group (52.6 ± 6.8 ms) were significantly higher than those of healthy subjects (44.9 ± 2.8 ms, p < 0.001) and fatty liver group (45.0 ± 3.5 ms, p < 0.001). Mean liver T1rho values were similar between healthy subjects and fatty liver group (p = 0.999). PDFF values in the fatty liver group (16.07 ± 10.59%) were significantly higher than those of healthy subjects (1.43 ± 1.36%, p < 0.001) and fibrosis group (1.07 ± 1.06%, p < 0.001). PDFF values were similar in healthy subjects and fibrosis group (p = 0.984). Mean T1rho values performed well to detect fibrosis at a threshold of 49.5 ms (area under the ROC curve, 0.855), had a moderate correlation with liver stiffness (r = 0.671, p = 0.012), and no correlation with PDFF, T2* values, subject age, or body mass index (p > 0.05). T1rho MRI is useful for noninvasive detection of liver fibrosis, and may not be affected with the presence of fatty liver.

Chronic aerobic exercise training alleviates myocardial fibrosis in aged rats through restoring bioavailability of hydrogen sulfide.

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Ma, Ning; Liu, Hong-Mei; Xia, Ting; Liu, Jian-Dong; Wang, Xiao-Ze

2018-06-02

Age-related fibrosis is attenuated by aerobic exercise; however, little is known concerning the underlying molecular mechanism. To address this question, aged rats were given moderate-intensity exercise for 12 weeks. After exercise in aged rats, hydrogen sulfide (H2S) levels in plasma and heart increased 39.8% and 90.9%, respectively. Exercise upregulated expression of cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) in heart of aged rats. Furthermore, aged rats were given moderate-intensity exercise for 12 weeks or treated with NaHS (intraperitoneal injection of 0.1 ml/kg/day of 0.28 mol/l NaHS). After exercise in aged rats, Masson-trichrome staining area decreased 34.8% and myocardial hydroxyproline levels decreased 29.6%. Exercise downregulated expression of collagen-I and α-SMA in heart of aged rats. Exercise in aged rats reduced malondialdehyde levels in plasma and heart and 3-nitrotyrosine in heart. Exercise in aged rats reduced mRNA and protein expression of CHOP, GRP78, and XBP1. Exercise also reduced mRNA and protein expression of IL-6 and MCP-1 and suppressed activation of JNK in aging heart. Similar effects were demonstrated in aged rats treated with NaHS. Collectively, exercise restored bioavailability of hydrogen sulfide in the heart of aged rats, which partly explained the benefits of exercise against myocardial fibrosis of aged population.

Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

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Chen Yi Mei, Swee Lin G; Thompson, Alexander J; Christensen, Britt; Cunningham, Georgina; McDonald, Lucy; Bell, Sally; Iser, David; Nguyen, Tin; Desmond, Paul V

2017-01-01

Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart. CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment. 131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62) years with median estimated duration of infection 33-years (IQR 29-38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p

Adverse fibrosis in the aging heart depends on signaling between myeloid and mesenchymal cells; role of inflammatory fibroblasts.

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Cieslik, Katarzyna A; Trial, JoAnn; Crawford, Jeffrey R; Taffet, George E; Entman, Mark L

2014-05-01

Aging has been associated with adverse fibrosis. Here we formulate a new hypothesis and present new evidence that unresponsiveness of mesenchymal stem cells (MSC) and fibroblasts to transforming growth factor beta (TGF-β), due to reduced expression of TGF-β receptor I (TβRI), provides a foundation for cardiac fibrosis in the aging heart via two mechanisms. 1) TGF-β promotes expression of Nanog, a transcription factor that retains MSC in a primitive state. In MSC derived from the aging heart, Nanog expression is reduced and therefore MSC gradually differentiate and the number of mesenchymal fibroblasts expressing collagen increases. 2) As TGF-β signaling pathway components negatively regulate transcription of monocyte chemoattractant protein-1 (MCP-1), a reduced expression of TβRI prevents aging mesenchymal cells from shutting down their own MCP-1 expression. Elevated MCP-1 levels that originated from MSC attract transendothelial migration of mononuclear leukocytes from blood to the tissue. MCP-1 expressed by mesenchymal fibroblasts promotes further migration of monocytes and T lymphocytes away from the endothelial barrier and supports the monocyte transition into macrophages and finally into myeloid fibroblasts. Both myeloid and mesenchymal fibroblasts contribute to fibrosis in the aging heart via collagen synthesis. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium ". © 2013. Published by Elsevier Ltd. All rights reserved.

Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.

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Schulman, Ivonne Hernandez; Zhou, Ming-Sheng; Treuer, Adriana V; Chadipiralla, Kiranmai; Hare, Joshua M; Raij, Leopoldo

2010-01-01

The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging. Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats. Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats. Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly. Copyright © 2010 S. Karger AG, Basel.

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

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

2018-04-11

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

MFAP4: a candidate biomarker for hepatic and pulmonary fibrosis?

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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.

Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

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Mora, Ana L.; Rojas, Mauricio; Pardo, Annie; Selman, Moises

2018-01-01

Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges. As ageing is a major risk factor for IPF, age-related cell perturbations such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis and mitochondrial dysfunction are becoming targets of interest for IPF therapy. In this Review, we discuss current and emerging therapies for IPF, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches. PMID:29081515

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

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

2018-02-19

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

Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

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Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Alam, Md Ashraful

2015-01-01

We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

Subjective Age in Early Adolescence: Relationships with Chronological Age, Pubertal Timing, Desired Age, and Problem Behaviors

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Hubley, Anita M.; Arim, Rubab G.

2012-01-01

Subjective age generally refers to the age that one feels. In a cross-sectional questionnaire study of 245 adolescents ages 10-14 years, we examined (a) whether, and when, a cross-over in subjective age occurs, (b) differences in subjective age among pubertal timing groups, (c) correlations between subjective age and each of desired age and five…

Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

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Swee Lin G Chen Yi Mei

Full Text Available Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR in people with chronic hepatitis C (CHC infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM using transient elastography [FibroScan] were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa or advanced (METAVIR F3-4/ LSM >9.5 kPa. The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2 to advanced fibrosis at follow-up liver fibrosis assessment.131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62 years with median estimated duration of infection 33-years (IQR 29-38. At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17. 109 (83% participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002. The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343. However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F

Drug- and radiation-induced pulmonary fibrosis

International Nuclear Information System (INIS)

Uthgenannt, H.

1976-01-01

These two forms of pulmonary fibrosis which according to their type have nothing to do with one another, are presented as they are well suited to clarify the problems of the diagnosis of pulmonary fibrosis which is not a fixed concept for the pathologists. The frequent discrepancy found between the subjective clinical symptoms, clinical findings and X-ray and morphological pictures is indicated. (MG) [de

Outcome in cystic fibrosis liver disease.

LENUS (Irish Health Repository)

Rowland, Marion

2011-01-01

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

Obesity, metabolic dysfunction and cardiac fibrosis: pathophysiologic pathways, molecular mechanisms and therapeutic opportunities

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Cavalera, Michele; Wang, Junhong; Frangogiannis, Nikolaos G

2014-01-01

Cardiac fibrosis is strongly associated with obesity and metabolic dysfunction and may contribute to the increased incidence of heart failure, atrial arrhythmias and sudden cardiac death in obese subjects. Our review discusses the evidence linking obesity and myocardial fibrosis in animal models and human patients, focusing on the fundamental pathophysiologic alterations that may trigger fibrogenic signaling, the cellular effectors of fibrosis and the molecular signals that may regulate the fibrotic response. Obesity is associated with a wide range of pathophysiologic alterations (such as pressure and volume overload, metabolic dysregulation, neurohumoral activation and systemic inflammation); their relative role in mediating cardiac fibrosis is poorly defined. Activation of fibroblasts likely plays a major role in obesity-associated fibrosis; however, inflammatory cells, cardiomyocytes and vascular cells may also contribute to fibrogenic signaling. Several molecular processes have been implicated in regulation of the fibrotic response in obesity. Activation of the Renin-Angiotensin-Aldosterone System, induction of Transforming Growth Factor-β, oxidative stress, advanced glycation end-products (AGEs), endothelin-1, Rho-kinase signaling, leptin-mediated actions and upregulation of matricellular proteins (such as thrombospondin-1) may play a role in the development of fibrosis in models of obesity and metabolic dysfunction. Moreover, experimental evidence suggests that obesity and insulin resistance profoundly affect the fibrotic and remodeling response following cardiac injury. Understanding the pathways implicated in obesity-associated fibrosis may lead to development of novel therapies to prevent heart failure and to attenuate post-infarction cardiac remodeling in obese patients. PMID:24880146

Variation in Subjective Aging by Sexual Minority Status.

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Barrett, Anne; Barbee, Harry

2017-06-01

The past few decades have seen increased scholarly attention to gay and lesbian individuals' aging experiences; however, few studies examine differences in subjective aging by sexual minority status. We identify four perspectives on the association between sexual minority status and subjective aging-double jeopardy, crisis competence, gender interactive, and limited salience perspectives. We examine each perspective's predictions using data from the first wave of Midlife in the United States (1995-1996; MIDUS). Ordinary least square regression models reveal strongest support for the limited salience perspective, suggesting that sexual minority status has weaker effects on subjective aging than do other social factors, such as age, health, and gender. However, some results provide support for the gender interactive perspective, positing that the effect of sexual minority status on subjective aging varies by gender. Our study provides an organizational framework of theoretical perspectives that can guide further examinations of variation in aging experiences by sexual minority status.

Exhaled nitric oxide in paediatric asthma and cystic fibrosis.

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Lundberg, J O; Nordvall, S L; Weitzberg, E; Kollberg, H; Alving, K

1996-01-01

Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be useful in non-invasive diagnosis and monitoring of inflammatory airway diseases. PMID:8984919

Subjective age and personality development: a 10-year study.

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Stephan, Yannick; Sutin, Angelina R; Terracciano, Antonio

2015-04-01

Personality theory and research typically focus on chronological age as a key indicator of personality development. This study examines whether the subjective experience of age is an alternative marker of the biomedical and psychosocial factors that contribute to individual differences in personality development. The present study uses data from the Midlife in the United States longitudinal survey (N = 3,617) to examine how subjective age is associated with stability and change in personality and the dynamic associations between subjective age and personality traits over a 10-year period. Regression analyses indicated that a younger subjective age at baseline was associated with increases in Openness, Conscientiousness, and Agreeableness; correlated changes were also found. The rank-order stability of Extraversion and Openness and overall profile consistency were higher among those with a younger subjective age at baseline and were also associated with the rate of subjective aging over time. The present study reveals that beyond chronological age, the age an individual feels is related to changes in characteristic ways of thinking, feeling, and behaving over time. © 2014 Wiley Periodicals, Inc.

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.)

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

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Charles C. Reilly

2016-03-01

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

Idiopathic Pulmonary Fibrosis: The Association between the Adaptive Multiple Features Method and Fibrosis Outcomes.

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Salisbury, Margaret L; Lynch, David A; van Beek, Edwin J R; Kazerooni, Ella A; Guo, Junfeng; Xia, Meng; Murray, Susan; Anstrom, Kevin J; Yow, Eric; Martinez, Fernando J; Hoffman, Eric A; Flaherty, Kevin R

2017-04-01

Adaptive multiple features method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns. To evaluate AMFM and visual quantification of HRCT patterns and their relationship with disease progression in idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal lung densities were measured by AMFM and three radiologists, documenting baseline disease extent and postbaseline change. Disease progression includes composite mortality, hospitalization, and 10% FVC decline. Agreement between visual and AMFM measurements was moderate for GGR (Pearson's correlation r = 0.60, P fibrosis (as measured by GGR densities) is independently associated with elevated hazard for disease progression. Postbaseline change in AMFM-measured and visually measured GGR densities are modestly correlated with change in FVC. AMFM-measured fibrosis is an automated adjunct to existing prognostic markers and may allow for study enrichment with subjects at increased disease progression risk.

Lipolysis stimulating peptides of potato protein hydrolysate effectively suppresses high-fat-diet-induced hepatocyte apoptosis and fibrosis in aging rats

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Wen-Dee Chiang

2016-07-01

Full Text Available Background: Non-alcoholic fatty liver disease (NAFLD is one of the most common outcomes of obesity and is characterized by the accumulation of triglycerides, increased tissue apoptosis, and fibrosis. NAFLD is more common among elderly than in younger age groups, and it causes serious hepatic complications. Objective: In this study, alcalase treatment derived potato protein hydrolysate (APPH with lipolysis-stimulating property has been evaluated for its efficiency to provide hepato-protection in a high-fat-diet (HFD-fed aging rats. Design: Twenty-four-month-old SD rats were randomly divided into six groups (n=8: aged rats fed with standard chow, HFD-induced aged obese rats, HFD with low-dose (15 mg/kg/day APPH treatment, HFD with moderate (45 mg/kg/day APPH treatment, HFD with high (75 mg/kg/day APPH treatment, and HFD with probucol. Results: APPH was found to reduce the NAFLD-related effects in rat livers induced by HFD and all of the HFD-fed rats exhibited heavier body weight than those with control chow diet. However, the HFD-induced hepatic fat accumulation was effectively attenuated in rats administered with low (15 mg/kg/day, moderate (45 mg/kg/day, and high (75 mg/kg/day doses of APPH. APPH oral administration also suppressed the hepatic apoptosis- and fibrosis-related proteins induced by HFD. Conclusions: Our results thus indicate that APPH potentially attenuates hepatic lipid accumulation and anti-apoptosis and fibrosis effects in HFD-induced rats. APPH may have therapeutic potential in the amelioration of NAFLD liver damage.

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

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Chia-Chi Wang

2015-10-01

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

The Processes and Mechanisms of Cardiac and Pulmonary Fibrosis

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Lucy A. Murtha

2017-10-01

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

Shared genetic effects between hepatic steatosis and fibrosis: A prospective twin study

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Cui, Jeffrey; Chen, Chi-Hua; Lo, Min-Tzu; Schork, Nicholas; Bettencourt, Ricki; Gonzalez, Monica P; Bhatt, Archana; Hooker, Jonathan; Shaffer, Katherine; Nelson, Karen E; Long, Michelle T; Brenner, David A; Sirlin, Claude B; Loomba, Rohit

2016-01-01

Introduction Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic risk factors including hypertension and dyslipidemia, and may progress to liver fibrosis. Previous studies have shown that hepatic steatosis and fibrosis are heritable but whether they have a significant shared gene effect is unknown. This study aimed to examine the shared gene effects between hepatic steatosis, fibrosis, and their associations with metabolic risk factors. Methods This is a cross-sectional analysis of a prospective cohort of well-characterized, community-dwelling twins (45 monozygotic, 20 dizygotic twin pairs, 130 total subjects) from Southern California. Hepatic steatosis was assessed with MRI-proton density fat fraction (MRI-PDFF) and hepatic fibrosis was assessed with magnetic resonance elastography (MRE). A standard bivariate twin AE model was used to estimate the proportion of phenotypic variance between two phenotypes accounted for by additive genetic effects (A) and individual-specific environmental effects (E). Genetic correlations (rG) estimated from this model represent the degree to which the genetic determinants of two phenotypes overlap. Results The mean (±SD) age and BMI were 47.1 (±21.9) years and 26.9 (±6.5) kg/m2, respectively. 20% (26/130) of the cohort had hepatic steatosis (MRI-PDFF ≥5%) and 8.2% (10/122) had hepatic fibrosis (MRE ≥3Kpa). Blood pressure (systolic and diastolic), triglycerides, glucose, homeostatic model assessment of insulin resistance (HOMA-IR), insulin, hemoglobin A1c (HbA1c), and low high-density lipoprotein (HDL) had significant shared gene effects with hepatic steatosis. Triglycerides, glucose, HOMA-IR, insulin, HbA1c, and low HDL had significant shared gene effects with hepatic fibrosis. Hepatic steatosis and fibrosis had a highly significant shared gene effect of 0.756 (95% CI: 0.716–1, psteatosis pathogenesis may also be involved with fibrosis pathogenesis. PMID:27315352

Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

International Nuclear Information System (INIS)

Bitterman, P.B.; Rennard, S.I.; Keogh, B.A.; Wewers, M.D.; Adelberg, S.; Crystal, R.G.

1986-01-01

We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known

Idiopathic Pulmonary Fibrosis: Data-driven Textural Analysis of Extent of Fibrosis at Baseline and 15-Month Follow-up.

Science.gov (United States)

Humphries, Stephen M; Yagihashi, Kunihiro; Huckleberry, Jason; Rho, Byung-Hak; Schroeder, Joyce D; Strand, Matthew; Schwarz, Marvin I; Flaherty, Kevin R; Kazerooni, Ella A; van Beek, Edwin J R; Lynch, David A

2017-10-01

Purpose To evaluate associations between pulmonary function and both quantitative analysis and visual assessment of thin-section computed tomography (CT) images at baseline and at 15-month follow-up in subjects with idiopathic pulmonary fibrosis (IPF). Materials and Methods This retrospective analysis of preexisting anonymized data, collected prospectively between 2007 and 2013 in a HIPAA-compliant study, was exempt from additional institutional review board approval. The extent of lung fibrosis at baseline inspiratory chest CT in 280 subjects enrolled in the IPF Network was evaluated. Visual analysis was performed by using a semiquantitative scoring system. Computer-based quantitative analysis included CT histogram-based measurements and a data-driven textural analysis (DTA). Follow-up CT images in 72 of these subjects were also analyzed. Univariate comparisons were performed by using Spearman rank correlation. Multivariate and longitudinal analyses were performed by using a linear mixed model approach, in which models were compared by using asymptotic χ 2 tests. Results At baseline, all CT-derived measures showed moderate significant correlation (P pulmonary function. At follow-up CT, changes in DTA scores showed significant correlation with changes in both forced vital capacity percentage predicted (ρ = -0.41, P pulmonary function (P fibrosis at CT yields an index of severity that correlates with visual assessment and functional change in subjects with IPF. © RSNA, 2017.

The many ways sputum flows - Dealing with high within-subject variability in cystic fibrosis sputum rheology.

Science.gov (United States)

Radtke, Thomas; Böni, Lukas; Bohnacker, Peter; Fischer, Peter; Benden, Christian; Dressel, Holger

2018-08-01

We evaluated test-retest reliability of sputum viscoelastic properties in clinically stable patients with cystic fibrosis (CF). Data from a prospective, randomized crossover study was used to determine within-subject variability of sputum viscoelasticity (G', storage modulus and G", loss modulus at 1 and 10 rad s -1 ) and solids content over three consecutive visits. Precision of sputum properties was quantified by within-subject standard deviation (SD ws ), coefficient of variation (CV) and intraclass correlation coefficients (ICC). Fifteen clinically stable adults with CF (FEV 1 range 24-94% predicted) were included. No differences between study visits (mean ± SD 8 ± 2 days) were observed for any sputum rheology measure. CV's for G', G" and solids content ranged between 40.3-45.3% and ICC's between 0.21-0.42 indicating poor to fair test-retest reliability. Short-term within-subject variability of sputum properties is high in clinically stable adults with CF. Investigators applying shear rheology experiments in future prospective studies should consider using multiple measurements aiming to increase precision of sputum rheological outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Cost-Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

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Gini, Andrea; Zauber, Ann G; Cenin, Dayna R; Omidvari, Amir-Houshang; Hempstead, Sarah E; Fink, Aliza K; Lowenfels, Albert B; Lansdorp-Vogelaar, Iris

2017-12-27

Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared to the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. We adjusted the existing Microsimulation Screening Analysis-Colon microsimulation model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess whether optimal screening strategies would change. Colonoscopy every 5 years, starting at age 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in population is not clear. Using a Microsimulation Screening Analysis-Colon microsimulation model, we found screening of patients with cystic fibrosis for CRC to be cost-effective. Due to the higher risk in these patients for CRC, screening should start at an earlier age with a shorter screening interval. The findings of this study

Dental enamel defects in Italian children with cystic fibrosis: an observational study.

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Ferrazzano, G F; Sangianantoni, G; Cantile, T; Amato, I; Orlando, S; Ingenito, A

2012-03-01

The relationship between cystic fibrosis (CF) and caries experience has already been explored, but relatively little information is available on dental enamel defects prevalence among children affected by cystic fibrosis. The aim of this study was to investigate this issue in deciduous and permanent teeth of children with CF resident in southern Italy. This cross sectional observational study was undertaken between October 2009 and March 2010. 88 CF patients and 101 healthy age-matched participated in this study. The prevalence of dental enamel defects was calculated using a modified Developmental Defects of Enamel (DDE) index. The comparison of dental enamel defects prevalence among groups was carried out using regression binary logistic analysis. In the CF subjects there was a higher prevalence (56%) of enamel defects in comparison to the healthy group (22%). The most prevalent enamel defect was hypoplasia with loss of enamel (23% of CF patients vs 1 1/2% of control group) in permanent teeth. This study confirms that children with cystic fibrosis are at increased risk of developing hypoplastic defects on their permanent teeth.

Prospective comparison of magnetic resonance imaging to transient elastography and serum markers for liver fibrosis detection.

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Dyvorne, Hadrien A; Jajamovich, Guido H; Bane, Octavia; Fiel, M Isabel; Chou, Hsin; Schiano, Thomas D; Dieterich, Douglas; Babb, James S; Friedman, Scott L; Taouli, Bachir

2016-05-01

Establishing accurate non-invasive methods of liver fibrosis quantification remains a major unmet need. Here, we assessed the diagnostic value of a multiparametric magnetic resonance imaging (MRI) protocol including diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE)-MRI and magnetic resonance elastography (MRE) in comparison with transient elastography (TE) and blood tests [including ELF (Enhanced Liver Fibrosis) and APRI] for liver fibrosis detection. In this single centre cross-sectional study, we prospectively enrolled 60 subjects with liver disease who underwent multiparametric MRI (DWI, DCE-MRI and MRE), TE and blood tests. Correlation was assessed between non-invasive modalities and histopathologic findings including stage, grade and collagen content, while accounting for covariates such as age, sex, BMI, HCV status and MRI-derived fat and iron content. ROC curve analysis evaluated the performance of each technique for detection of moderate-to-advanced liver fibrosis (F2-F4) and advanced fibrosis (F3-F4). Magnetic resonance elastography provided the strongest correlation with fibrosis stage (r = 0.66, P fibrosis (F2-F4), AUCs were 0.78, 0.82, 0.72, 0.79, 0.71 for MRE, TE, DCE-MRI, DWI and APRI, respectively. For detection of advanced fibrosis (F3-F4), AUCs were 0.94, 0.77, 0.79, 0.79 and 0.70, respectively. Magnetic resonance elastography provides the highest correlation with histopathologic markers and yields high diagnostic performance for detection of advanced liver fibrosis and cirrhosis, compared to DWI, DCE-MRI, TE and serum markers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multiple-Breath Washout Outcomes Are Sensitive to Inflammation and Infection in Children with Cystic Fibrosis.

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Ramsey, Kathryn A; Foong, Rachel E; Grdosic, Jasmine; Harper, Alana; Skoric, Billy; Clem, Charles; Davis, Miriam; Turkovic, Lidija; Stick, Stephen M; Davis, Stephanie D; Ranganathan, Sarath C; Hall, Graham L

2017-09-01

The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. The lung clearance index is increased in the presence of lower respiratory tract inflammation and infection in infants with cystic fibrosis; however, the associations during the preschool years are unknown. We assessed the ability of the lung clearance index to detect the presence and extent of lower respiratory tract inflammation and infection in preschool children with cystic fibrosis. Ventilation distribution outcomes were assessed at 82 visits with 58 children with cystic fibrosis and at 38 visits with 31 healthy children aged 3-6 years. Children with cystic fibrosis also underwent bronchoalveolar lavage fluid collection for detection of lower respiratory tract inflammation and infection. Associations between multiple-breath washout indices and the presence and extent of airway inflammation and infection were assessed using linear mixed effects models. Lung clearance index was elevated in children with cystic fibrosis (mean [SD], 8.00 [1.45]) compared with healthy control subjects (6.67 [0.56]). In cystic fibrosis, the lung clearance index was elevated in individuals with lower respiratory tract infections (difference compared with uninfected [95% confidence interval], 0.62 [0.06, 1.18]) and correlated with the extent of airway inflammation. These data suggest that the lung clearance index may be a useful surveillance tool for monitoring the presence and extent of lower airway inflammation and infection in preschool children with cystic fibrosis.

Serum biomarkers and transient elastography as predictors of advanced liver fibrosis in a United States cohort: the Boston children's hospital experience.

Science.gov (United States)

Lee, Christine K; Perez-Atayde, Antonio R; Mitchell, Paul D; Raza, Roshan; Afdhal, Nezam H; Jonas, Maureen M

2013-10-01

To evaluate and compare the ability of serum hyaluronic acid (HA) and human cartilage glycoprotein-39 (YKL-40) values, as well as transient elastography (TE) findings, to predict advanced hepatic fibrosis in a cohort from a single pediatric center. Subjects who underwent liver biopsy analysis within 12 months before enrollment were eligible for this prospective study. HA and YKL-40 measurements were obtained within 1 month of TE. A METAVIR score of F3 or F4 was considered to indicate advanced fibrosis. A total of 128 patients (51% males) aged 1.4 months to 27.6 years (22% aged blood tests and TE. For the prediction of advanced fibrosis, the area under the receiver operating characteristic curve (AUC) values were 0.83 for TE, 0.72 for HA, and 0.52 for YKL-40. The AUC of 0.83 for TE was statistically significantly greater than the AUCs for HA (P = .03) and YKL-40 (P fibrosis were 8.6 kPa for TE (P fibrosis (P = .15). In this study, which evaluated TE, HA, and YKL-40 to predict liver fibrosis in children in the US, YKL-40 had no predictive value and TE was superior to HA, but the addition of HA did not improve the performance of TE. Our data suggest that TE and HA may be useful noninvasive tools for assessing liver fibrosis in children. Copyright © 2013 Mosby, Inc. All rights reserved.

Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections.

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Hisert, Katherine B; Heltshe, Sonya L; Pope, Christopher; Jorth, Peter; Wu, Xia; Edwards, Rachael M; Radey, Matthew; Accurso, Frank J; Wolter, Daniel J; Cooke, Gordon; Adam, Ryan J; Carter, Suzanne; Grogan, Brenda; Launspach, Janice L; Donnelly, Seamas C; Gallagher, Charles G; Bruce, James E; Stoltz, David A; Welsh, Michael J; Hoffman, Lucas R; McKone, Edward F; Singh, Pradeep K

2017-06-15

Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.

Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

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Gini, Andrea; Zauber, Ann G; Cenin, Dayna R; Omidvari, Amir-Houshang; Hempstead, Sarah E; Fink, Aliza K; Lowenfels, Albert B; Lansdorp-Vogelaar, Iris

2018-02-01

Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess if optimal screening strategies would change. Colonoscopy every 5 years, starting at an age of 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in this population is not clear. Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT

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

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

2000-12-15

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

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

Syndecans in heart fibrosis.

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

2016-09-01

the contents of the current review on syndecans in cardiac fibrosis. The heart is subjected to various forms of pathological stimuli, e.g., myocardial infarction, hypertension, valvular stenosis, infection, or an inherited genetic mutation, triggering responses in cells resident in the heart. Here, we focus on the responses of cardiac fibroblasts directing changes in the extracellular matrix resulting in cardiac fibrosis. A family of four transmembrane proteoglycans, syndecan-1 to -4, is expressed in the cell membrane of cardiac fibroblasts and is generally up-regulated in response to the above-mentioned pathological stimuli. Syndecans carry glycosaminoglycan chains on their extracellular domain, binding a plethora of molecules involved in fibrosis, e.g., growth factors, cytokines, immune cell adhesion proteins, and pathogens. Syndecans have a short cytoplasmic tail involved in pro-fibrotic signaling. The signaling and cellular processes governed by syndecans in the heart in response to pathological stimuli regulate important aspects of extracellular matrix remodeling and fibrosis and have mainly been studied in cardiac remodeling in response to cardiac infarction and pressure overload. In general, adequate timing and the quantity and quality of fibrosis are absolutely crucial for heart function and survival, determining cardiac stiffness, contractility, compliance, probability of rupture, dilation, and diastolic and systolic function. Syndecan-1 and -4 have mainly been studied in the heart and are discussed in this review (LV left ventricle).

Cystic fibrosis-related diabetes: a distinct condition.

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Cano Megías, Marta; González Albarrán, Olga

2015-01-01

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

Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis.

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Kannengiesser, Caroline; Borie, Raphael; Ménard, Christelle; Réocreux, Marion; Nitschké, Patrick; Gazal, Steven; Mal, Hervé; Taillé, Camille; Cadranel, Jacques; Nunes, Hilario; Valeyre, Dominique; Cordier, Jean François; Callebaut, Isabelle; Boileau, Catherine; Cottin, Vincent; Grandchamp, Bernard; Revy, Patrick; Crestani, Bruno

2015-08-01

Pulmonary fibrosis is a fatal disease with progressive loss of respiratory function. Defective telomere maintenance leading to telomere shortening is a cause of pulmonary fibrosis, as mutations in the telomerase component genes TERT (reverse transcriptase) and TERC (RNA component) are found in 15% of familial pulmonary fibrosis (FPF) cases. However, so far, about 85% of FPF remain genetically uncharacterised.Here, in order to identify new genetic causes of FPF, we performed whole-exome sequencing, with a candidate-gene approach, of 47 affected subjects from 35 families with FPF without TERT and TERC mutations.We identified heterozygous mutations in regulator of telomere elongation helicase 1 (RTEL1) in four families. RTEL1 is a DNA helicase with roles in DNA replication, genome stability, DNA repair and telomere maintenance. The heterozygous RTEL1 mutations segregated as an autosomal dominant trait in FPF, and were predicted by structural analyses to severely affect the function and/or stability of RTEL1. In agreement with this, RTEL1-mutated patients exhibited short telomeres in comparison with age-matched controls.Our results provide evidence that heterozygous RTEL1 mutations are responsible for FPF and, thereby, extend the clinical spectrum of RTEL1 deficiency. Thus, RTEL1 enlarges the number of telomere-associated genes implicated in FPF. Copyright ©ERS 2015.

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.

Multidimensional clinical phenotyping of an adult cystic fibrosis patient population.

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Douglas J Conrad

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

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

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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

Association between noninvasive fibrosis markers and chronic kidney disease among adults with nonalcoholic fatty liver disease.

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Giorgio Sesti

Full Text Available Evidence suggests that nonalcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH are associated with an increased risk of chronic kidney disease (CKD. In this study we aimed to evaluate whether the severity of liver fibrosis estimated by NAFLD fibrosis score is associated with higher prevalence of CKD in individuals with NAFLD. To this end NAFLD fibrosis score and estimated glomerular filtration rate (eGFR were assessed in 570 White individuals with ultrasonography-diagnosed NAFLD. As compared with subjects at low probability of liver fibrosis, individuals at high and intermediate probability showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein, fibrinogen, uric acid and lower insulin-like growth factor-1 levels. Individuals at high and intermediate probability of liver fibrosis have lower eGFR after adjustment for gender, smoking, glucose tolerance status, homeostasis model assessment index of insulin resistance (HOMA-IR index, diagnosis of metabolic syndrome, statin therapy, anti-diabetes and anti-hypertensive treatments (P = 0.001. Individuals at high probability of liver fibrosis had a 5.1-fold increased risk of having CKD (OR 5.13, 95%CI 1.13-23.28; P = 0.03 as compared with individuals at low probability after adjustment for age, gender, and BMI. After adjustment for glucose tolerance status, statin therapy, and anti-hypertensive treatment in addition to gender, individuals at high probability of liver fibrosis had a 3.9-fold increased risk of CKD (OR 3.94, 95%CI 1.11-14.05; P = 0.03 as compared with individuals at low probability. In conclusion, advanced liver fibrosis, determined by noninvasive fibrosis markers, is associated with CKD independently from other known factors.

Effects of puberty on cystic fibrosis related pulmonary exacerbations in women versus men.

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Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

2014-01-01

Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre- and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. © 2013 Wiley Periodicals, Inc.

Laboratory confirmation of the diagnosis of cystic fibrosis.

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Tocci, P M; McKey, R M

1976-11-01

The recent commercial introduction of a method for detecting albumin in meconium makes screening for cystic fibrosis feasible for many hospitals. If the tests is adopted, confirmatory tests should be available. Quantitative analyses of sweat for sodium by flame photometry and for chloride by silver titration and ion-sleective electrodes are now used as confirmatory tests. We compare results of these confirmatory methods applied to presons with cystic fibrosis, respiratory disorders, or digestive disorders, and to control subjects.

An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis.

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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.

IMMUNE RESPONSE TO EXTRACELLULAR MATRIX COLLAGEN IN CHRONIC HEPATITIS C INDUCED LIVER FIBROSIS

OpenAIRE

Borg, Brian B.; Seetharam, Anil; Subramanian, Vijay; Ilias, Haseeb; Lisker–Melman, Mauricio; Korenblat, Kevin; Anderson, Christopher; Shenoy, Surendra; Chapman, William C.; Crippin, Jeffrey S.; Mohanakumar, Thalachallour

2011-01-01

Hepatitis C Virus (HCV) infection and recurrence post-transplant (OLT) is associated with extracellular matrix (ECM) components remodeling, particularly collagen (Col), leading to fibrosis. Our aim was to determine whether development of antibodies (Abs) to self antigen Col in HCV infection correlates with fibrosis stage and peripheral cytokine response. Chronic HCV patients, those with recurrence after OLT undergoing biopsy and healthy control subjects were enrolled. HCV subjects (n=70) were...

Introduction to Pulmonary Fibrosis

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... 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 ...

Glycoprotein YKL-40 Levels in Plasma Are Associated with Fibrotic Changes on HRCT in Asbestos-Exposed Subjects

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Tuija Väänänen

2017-01-01

Full Text Available YKL-40 is a chitinase-like glycoprotein produced by alternatively activated macrophages that are associated with wound healing and fibrosis. Asbestosis is a chronic asbestos-induced lung disease, in which injury of epithelial cells and activation of alveolar macrophages lead to enhanced collagen production and fibrosis. We studied if YKL-40 is related to inflammation, fibrosis, and/or lung function in subjects exposed to asbestosis. Venous blood samples were collected from 85 men with moderate or heavy occupational asbestos exposure and from 28 healthy, age-matched controls. Levels of plasma YKL-40, CRP, IL-6, adipsin, and MMP-9 were measured with enzyme-linked immunosorbent assay (ELISA. Plasma YKL-40 levels were significantly higher in subjects with asbestosis (n=19 than in those with no fibrotic findings in HRCT following asbestos exposure (n=66 or in unexposed healthy controls. In asbestos-exposed subjects, plasma YKL-40 correlated negatively with lung function capacity parameters FVC (Pearson’s r −0.259, p=0.018 and FEV1 (Pearson’s r −0.240, p=0.028 and positively with CRP (Spearman’s rho 0.371, p<0.001, IL-6 (Spearman’s rho 0.314, p=0.003, adipsin (Spearman’s rho 0.459, p<0.001, and MMP-9 (Spearman’s rho 0.243, p=0.025. The present finding suggests YKL-40 as a biomarker associated with fibrosis and inflammation in asbestos-exposed subjects.

Personality, self-rated health, and subjective age in a life-span sample: the moderating role of chronological age.

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Stephan, Yannick; Demulier, Virginie; Terracciano, Antonio

2012-12-01

The present study tested whether chronological age moderates the association between subjective age and self-rated health and personality in a community-dwelling life-span sample (N = 1,016; age range: 18-91 years). Self-rated health, extraversion, and openness to experience were associated with a younger subjective age at older ages. Conscientious individuals felt more mature early in life. Conscientiousness, neuroticism, and agreeableness were not related to subjective age at older ages. These findings suggest that with aging self-rated health and personality traits are increasingly important for subjective age. 2013 APA, all rights reserved

Pentoxifylline therapy : A new adjunct in the treatment of oral submucous fibrosis

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Rajendran R

2006-01-01

Full Text Available OBJECTIVE : This study was designed to determine the effect of pentoxifylline (Trental on the clinical and pathologic course of oral submucous fibrosis. This drug is a methylxanthine derivative that has vasodilating properties and was envisaged to increase mucosal vascularity. STUDY DESIGN : This investigation was conducted as a randomized clinical trial incorporating a control group (Standard drug group SDG, multivitamin, and local heat therapy in comparison to pentoxifylline test cases (Experimental drug group EDG, 400mg 3 times daily, as coated, sustained release tablets. The stipulated treatment period was 7 months and a total of 29 cases of advanced fibrosis (14 test subjects and 15 age and sex matched diseased controls were included in this study and 100% compliance was reported at the end ofthe test period. RESULTS : Mild gastric irritation that could be managed by diet protocols was the only untoward symptom reported during this trial. Review of the patients and controls was done at an interval of 30 days and subjective and objective measurements were recorded. The follow up data at each visit with respect to each other and to base-line values was calibrated using a nonparametric test of Mann-Whitney (Kruskal-Wallis test. Significant comparisons with regard to improvement were recorded as objective criteria of mouth opening (t=11.285, p= 0.000, tongue protrusion (t= 3.898, p = 0.002, and relief from perioral fibrotic bands (p = 0.0001554. Subjective symptoms of intolerance to spices (p = 0.0063218, burning sensation of mouth (p = 0.0005797, tinnitus (p=0.000042, difficulty in swallowing (p=0.0000714. and difficulty in speech (p=0.0000020 were also recorded significant improvement at the end of the trial period. CONCLUSION : This pilot investigation points to the effectiveness of pentoxifylline as an adjunct therapy in the routine management of oral submucous fibrosis.

Pulmonary Fibrosis Foundation

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... 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 ...

Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated cardiac fibrosis.

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Black, Mary Jane; D'Amore, Angelo; Auden, Alana; Stamp, Laura; Osicka, Tanya; Panagiotopoulos, Sianna; Jerums, George

2010-01-01

Diabetes in human subjects is often associated with hypertension. The aim of this study was to examine the development of cardiac fibrosis following induction of type 1 diabetes in genetically hypertensive rats. Diabetes was induced by streptozotocin (STZ) injection in 8-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) for a duration of 16 or 24 weeks. Aged-matched, nondiabetic WKY and SHRs were used as controls. At termination of treatment, the rats were anaesthetized, hearts arrested in diastole and perfusion fixed. A comprehensive examination of cardiac fibrosis throughout the right and left ventricles was undertaken in picrosirius red-stained sections, using image analysis and by undertaking collagen type I and type III immunohistochemistry. Induction of diabetes in the SHRs led to a marked increase in the levels of interstitial fibrosis in the left ventricle plus septum (LV+S) at both 16 and 24 weeks duration (59% and 43% increase, respectively) and also in the right ventricle after 24 weeks duration of diabetes (35% increase compared to the nondiabetic SHR). Exacerbated perivascular fibrosis was also observed in the LV+S in the diabetic-hypertensive rats at the later time point. These effects of induction of diabetes were not observed in the normotensive strain. Our findings clearly demonstrate elevations in cardiac fibrosis when type 1 diabetes is combined with hypertension. Our findings thus stress the importance of closely monitoring both blood pressure and glucose levels in type 1 diabetic patients in order to prevent myocardial collagen deposition. Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Postinjection Muscle Fibrosis from Lupron

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Erica Everest

2015-01-01

Full Text Available We describe the case of a 6.5-year-old girl with central precocious puberty (CPP, which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP. She had left breast development at Tanner Stage 2, adult body odor, and mildly advanced bone age. In order to halt puberty and maximize adult height, she was prescribed a gonadotropin releasing hormone analog, the first line treatment for CPP. She was administered Lupron (leuprolide acetate Depot-Ped (3 months intramuscularly. After her second injection, she developed swelling and muscle pain at the injection site on her right thigh. She also reported an impaired ability to walk. She was diagnosed with muscle fibrosis. This is the first reported case of muscle fibrosis resulting from Lupron injection.

Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

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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.

Oral submucous fibrosis at pediatric age, now time to think: Series of two cases

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Gupta, Vinay K.; Malhotra, Seema; Patil, Ranjit; Tripathi, Anurag

2013-01-01

The younger generation is consuming areca nut and areca nut products, which is coming in the market with different multicolored attractive pouches and easily available in each and every corner of the road. For the children from the lower socioeconomic strata, areca nut use is rampant. Alarmingly, it has been seen that the highest period of risk for engaging in areca nut alone is between the ages of 5 and 12. Oral submucous fibrosis associated with areca nut in children is a great concern for the Society and the Government. Factors associated with this report for consuming areca nut are levels of awareness, household environment, peer pressure, low cost, easy availability etc. PMID:24049299

Accuracy of FibroScan for diagnosing liver fibrosis

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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.

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

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

2018-02-02

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

Assessment of hepatic fibrosis by fibroscan in egyptian chronic hemodialysis patients with chronic Hepatitis C (genotype 4: A single-center study

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Bahaa El-Din Moustafa Zayed

2017-01-01

Full Text Available Assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC can help to evaluate the long-term prognosis, complications of hepatitis C virus (HCV as well as eligibility for renal transplantation,. Our aim was to assess liver fibrosis in Egyptian hemodialysis (HD patients infected with CHC genotype 4 using a fibroscan. This cross-sectional observational study was conducted over two years on a cohort of 134 Egyptian patients on prevalent HD at Kasr Al Ainy Hospital. All patients were subjected to routine laboratory evaluation including, hepatitis B surface antigen, hepatitis B core antibody, hepatitis Be antigen, hepatitis C antibody (HCVAb and human immunodeficiency virus antibody, quantitative polymerase chain reaction (PCR for both HCV and hepatitis B virus (HBV, serum hyaluronic acid level, and alpha-fetoprotein (AFP. Fibroscan was performed on all HCV-positive patients. The mean age was 47.43 ± 12.65 years, 50.7% were male, and 49.3% were female. The most common causes of end-stage renal disease were hypertensive nephropathy (32.1% and diabetic nephropathy (18.7%. HCVAb was positive in 57.5% of the patients and HBV was positive in 3%. Forty HCV-positive patients (57.1% who underwent fibroscan had mild to significant fibrosis, and thirty patients (42.9% had advanced fibrosis. There was significant correlation between HCV PCR and duration on HD, number of blood transfusions, and hyaluronic acid (HA level. In addition, there was a significant correlation between serum HA and HD duration as well as liver fibrosis. No significant correlation was found between duration on HD and fibrosis stage (P = 0.619; also, no significant correlation was noted between the age of the patients and HA level or stage of fibrosis (P = 0.970. Fibro-scan is a simple noninvasive test that can be used to assess liver fibrosis in HD patients with CHC. Most of the study patients had mild to significant fibrosis.

[Combination of NAFLD Fibrosis Score and liver stiffness measurement for identification of moderate fibrosis stages (II & III) in non-alcoholic fatty liver disease].

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Drolz, Andreas; Wehmeyer, Malte; Diedrich, Tom; Piecha, Felix; Schulze Zur Wiesch, Julian; Kluwe, Johannes

2018-01-01

Non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent causes of chronic liver disease. Currently, therapeutic options for NAFLD patients are limited, but new pharmacologic agents are being investigated in the course of clinical trials. Because most of these studies are focusing on patients with fibrosis stages II and III (according to Kleiner), non-invasive identification of patients with intermediate fibrosis stages (II and III) is of increasing interest. Evaluation of NAFLD Fibrosis Score (NFS) and liver stiffness measurement (LSM) for prediction of fibrosis stages II/III. Patients with histologically confirmed NAFLD diagnosis were included in the study. All patients underwent a clinical and laboratory examination as well as a LSM prior to liver biopsy. Predictive value of NFS and LSM with respect to identification of fibrosis stages II/III was assessed. 134 NAFLD patients were included and analyzed. Median age was 53 (IQR 36 - 60) years, 55 patients (41 %) were female. 82 % of our patients were overweight/obese with typical aspects of metabolic syndrome. 84 patients (66 %) had liver fibrosis, 42 (50 %) advanced fibrosis. LSM and NFS correlated with fibrosis stage (r = 0.696 and r = 0.685, respectively; p stages II/III. If both criteria were met, probability of fibrosis stage II/III was 61 %. If none of the two criteria was met, chance for fibrosis stage II/III was only 6 % (negative predictive value 94 %). Combination of LSM and NFS enables identification of patients with significant probability of fibrosis stage II/III. Accordingly, these tests, especially in combination, may be a suitable screening tool for fibrosis stages II/III in NAFLD. The use of these non-invasive methods might also help to avoid unnecessary biopsies. © Georg Thieme Verlag KG Stuttgart · New York.

Ultrasound based evaluation of hepatic steatosis and fibrosis in hepatitis c non-responders

International Nuclear Information System (INIS)

Sohail, S.; Aziz, S.

2013-01-01

To determine the accuracy of ultrasound in the diagnosis and grading of steatosis and fibrosis in Hepatitis C (HCV) patients not responding to ribavarin-interferon therapy. Study Design: A cross-sectional, analytical study. Place and Duration of Study: Radiology Department, Civil Hospital, Karachi, from March 2008 to August 2010. Methodology: Patients with positive HCV RNA despite 24 weeks ribavarin-interferon therapy (non-responders) were subjected to ultrasound and biopsy prior to institution of pegylated interferon therapy for detection and grading of steatosis and fibrosis. Using histopathology as the gold standard, sensitivity, specificity, negative and positive predictive values for ultrasound were determined. Results: The sensitivity of ultrasound for hepatic steatosis was 90.9% for no steatosis (NS), 100% for moderate and gross steatosis and 84.4% for mild steatosis with 100% specificity. The senitivity for fibrosis was 25% for no fibrosis, 100% for mild fibrosis, 89.74% for moderate fibrosis and 100% for gross fibrosis. The overall accuracy for detection of steatosis was 95.39% and that for fibrosis was 98.02%. Hepatic vein showed increased dampening of flow with advancing grades of steatosis and fibrosis. Conclusion: Ultrasound has a high accuracy in the diagnosis and grading of steatosis and fibrosis in HCV nonresponders. Mild fibrosis may confound the diagnosis of mild steatosis. (author)

[Italian Cystic Fibrosis Registry. Report 2011-2014].

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Giordani, Barbara; Amato, Annalisa; Majo, Fabio; Ferrari, Gianluca; Quattrucci, Serena; Minicucci, Laura; Padoan, Rita; Floridia, Giovanna; Puppo Fornaro, Gianna; Taruscio, Domenica; Salvatore, Marco

2018-01-01

centre refer only to 2014. The present Report has been organized into 10 sections. 1. Demography - number of Italian patients with cystic fibrosis (CF) in 2014 was 4,981 and their median age was 20.4 years; estimated 2014 CF prevalence was 8.2/100,000 residents in Italy; on average, 52.1% of the patients were male and CF distribution showed higher frequency in patients aged from 7 to 35 years. On average, 53.7% of CF patients are aged more than 18 years. 2. Diagnoses - most of the CF patients were diagnosed before two years of age (around 66%); a significant proportion of patients (on average, 12%) was diagnosed in adult age. 3. New diagnoses - new diagnoses were 187 in 2011, 200 in 2012, 160 in 2013, and 135 in 2014. Estimated incidence was 1/4,052 live births in 2011; 1/4,313 in 2012; 1/5,189 in 2013 and 1/8,243 in 2014. 4. Genetics - 99.5% of patients was studied at the molecular level, with identification of 90.1% of Cystic Fibrosis Transmembrane Regulator CFTR mutations; [delta]508F was the most frequent mutation (44.8% in 2014). 5. Lung function - FEV₁ (Forced Expiratory Volume in the first second) scores progressively decreased shortly before the start of adult age, in accordance with the natural history of the disease. Most of the patients between 6 and 17 years of age reported a FEV₁ % ≥ 70% of the predicted value, while the proportion of patients with severe lung disease (FEV₁ % <40% of the predicted value) is <2% over the period 2011-2014. 6. Nutrition - most critical periods come out during the first 6 months of life and during adolescence. Prevalence of malnourished male aged 12-17 years decreases over the period 2011-2014; an increasing percentage of patient (both male and female) with a suboptimal body mass index value is observed among patients aged more than 18 years 7. Complications - the presence of missing data represents an obstacle in the correct evaluation of prevalence value of complications related to Italian patients within ICFR

Prevalence of dyslipidemia in adults with cystic fibrosis.

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Rhodes, Bronwen; Nash, Edward F; Tullis, Elizabeth; Pencharz, Paul B; Brotherwood, Michelle; Dupuis, Annie; Stephenson, Anne

2010-01-01

A high fat calorie diet is advocated for patients with cystic fibrosis (CF) however the lipid profiles of individuals with CF, including those with CF-related diabetes (CFRD), are not well studied. We conducted a retrospective review of adult CF patients attending St Michael's Hospital between January 2005 and December 2007. 334 patients (77% pancreatic insufficient (PI)) were included in the study. Mean HDL cholesterol was significantly lower in males (p201mg/dL(5.2mmol/L) (p195mg/dL(2.2mmol/L). Diabetes was diagnosed in 23% of subjects. Lipid profiles were similar between diabetics and non-diabetics. Total cholesterol and triglycerides both increased with increasing age and increasing BMI (pdiabetes and those without. Fasting lipids should be monitored in CF patients, particularly those with PS, older age, and high BMI. As survival in CF increases, the prevalence of dyslipidemia may increase resulting in clinically important complications.

Familial Pulmonary Fibrosis

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... 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 ...

Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to the periphery of the aging lung: a unifying hypothesis regarding etiology and pathogenesis.

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Leslie, Kevin O

2012-06-01

Idiopathic pulmonary fibrosis is a progressive, fatal lung disease occurring in older individuals. Despite 50 years of accrued data about the disease, little progress has been made in slowing functional loss or in decreasing patient mortality. To present a novel hypothesis on the etiology and pathogenesis of idiopathic pulmonary fibrosis. Published data are reviewed regarding the epidemiology, clinical presentation, natural history, radiologic findings, and pathologic findings in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis may be predisposed genetically to tractional injury to the peripheral lung. The result is recurrent damage to the epithelial-mesenchymal interface, preferentially at the outer edges of the basilar lung lobules where tractional stress is high during inspiration, compliance is relatively low, and there is a greater tendency for alveolar collapse at end-expiration. A distinctive "reticular network of injury" (the fibroblast focus) forms, attended by a prolonged phase of wound repair (tear and slow repair). Discrete areas of alveolar collapse are observed in scar at the periphery of the lung lobules. The cycle repeats over many years resulting in progressive fibrous remodeling and replacement of the alveoli in a lobule by bronchiolar cysts surrounded by scar (honeycomb lung). Abnormalities in surfactant function are proposed as a potential mechanism of initial lung damage. Age of onset may be a function of a required threshold of environmental exposures (eg, cigarette smoking) or other comorbid injury to the aging lung. Evidence supporting this hypothesis is presented and potential mechanisms are discussed. A potential role for contributing cofactors is presented.

Correlations between tests of aging in Hiroshima subjects: an attempt to define physiologic age

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Hollingsworth, J W; Hashizume, Asaji; Jablon, Seymour

1964-12-01

Nine physiologic functions which change with age were measured in 437 subjects during their regular visits to the Atomic Bomb Casualty Commission clinic in Hiroshima, Japan. This pilot study was undertaken to determine the feasibility of collecting such data in a population sample physiologic age score. Tests conducted consisted of: skin elasticity, systolic blood pressure, vital capacity, hand grip strength, light extinction time, vibrometer, visual activity, audiometry, and serum cholesterol. The study demonstrated that adequate sample data could be obtained, and that statistical treatment could construct a physiologic age for individual subjects. However, the tests were of limited value below age 40, and the validation of the concept of physiologic age requires eventual correlation with mortality. Since the ABCC program includes a highly accurate mortality survey, it is hoped that data on physiologic aging can be collected and eventually related to mortality. 11 references, 3 figures, 6 tables.

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

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Münevver Demir

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

Screening of preschool and school children for cystic fibrosis with the chloride electrode and neutron activation analysis. Part of a coordinated programme on medical applications of activation analysis

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Gurson, C.T.

1975-10-01

A screening study was performed on 9,685 infants and children between 0 and 7 years of age living in the city of Istanbul. 2,511 of the subjects (''normals'') were kindergarten and school children and the remainder were children who had been brought to the casualty outpatient departments of two large hospitals. The purposes of the investigation were twofold, first to determine the prevalence of cystic fibrosis in a normal versus a sick population of children, and second to compare sweat-chloride vis-a-vis nail-sodium as indicators of the disease. Sweat-chloride was determined in all subjects by the use of a chloride specific electrode; nail sodium was determined in 1122 subjects by neutron activation analysis. These measurements led to the identification of seven cystic fibrosis cases in the outpatient group (frequency = 0.1%) and none in the kindergarten/school group. Sweat-chloride gave 0.7% false positives and no false negatives; nailsodium gave 14.7% false positives and 0.1% false negatives. It is concluded that nail-sodium is a much less effective indicator of cystic fibrosis than sweat-chloride and its use can probably not be justified except in certain special circumstances. Furthermore it would appear that the screening of outpatient cases rather than the whole population of children is a more cost-effective method for the detection of cystic fibrosis

Barriers to adherence in cystic fibrosis

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Bregnballe, Vibeke; Schiøtz, Peter Oluf

2012-01-01

Danish patients with cystic fibrosis aged 14 to 25 years and their parents. Conclusions: The present study showed that the majority of adolescents with CF and their parents experienced barriers to treatment adherence. Patients and parents agreed that the three most common barriers encountered lack...

Age Effects on Upper Limb Kinematics Assessed by the REAplan Robot in Healthy Subjects Aged 3 to 93 Years.

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Gilliaux, Maxime; Lejeune, Thierry M; Sapin, Julien; Dehez, Bruno; Stoquart, Gaëtan; Detrembleur, Christine

2016-04-01

Kinematics is recommended for the quantitative assessment of upper limb movements. The aims of this study were to determine the age effects on upper limb kinematics and establish normative values in healthy subjects. Three hundred and seventy healthy subjects, aged 3-93 years, participated in the study. They performed two unidirectional and two geometrical tasks ten consecutive times with the REAplan, a distal effector robotic device that allows upper limb displacements in the horizontal plane. Twenty-six kinematic indices were computed for the four tasks. For the four tasks, nineteen of the computed kinematic indices showed an age effect. Seventeen indices (the accuracy, speed and smoothness indices and the reproducibility of the accuracy, speed and smoothness) improved in young subjects aged 3-30 years, showed stabilization in adults aged 30-60 years and declined in elderly subjects aged 60-93 years. Additionally, for both geometrical tasks, the speed index exhibited a decrease throughout life. Finally, a principal component analysis provided the relations between the kinematic indices, tasks and subjects' age. This study is the first to assess age effects on upper limb kinematics and establish normative values in subjects aged 3-93 years.

Assessment of Salivary Flow Rate and pH Among Areca Nut Chewers and Oral Submucous Fibrosis Subjects: A Comparative Study.

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Abdul Khader, Nishat Fatima; Dyasanoor, Sujatha

2015-09-01

To assess and compare the salivary flow rate (SFR) and salivary pH among areca nut chewers, oral submucous fibrosis (OSMF) patients and apparently healthy individuals. A comparative study was conducted to assess and compare the SFR and pH among 135 outpatients (45 areca nut chewers + 45 OSMF + 45 control) at The Oxford Dental College and Research Hospital, Bangalore, India. Subjects were interviewed using structural proforma and Modified Schirmer strips and pH paper were implemented for assessing SFR and pH respectively. Statistical analysis was done using IBM SPSS ver. 21.0 software. A statistically significant increase in SFR (35.7 mm at 3rd minutes) among areca nut group and a decrease in SFR among OSMF group (23.4 mm at 3rd minutes) when compared to apparently healthy subjects (30.7 mm at 3rd minutes). The mean pH among areca nut, OSMF and control groups was 6.76, 6.82, and 6.74 respectively with no statistical significance. The observation and findings of the study clearly showed hypersalivation among areca nut group and hyposalivation among OSMF group, with no significant change in salivary pH when compared to healthy subjects.

Retroperitoneal fibrosis with pancreatic involvement – radiological appearance

International Nuclear Information System (INIS)

Zielonko, Joanna; Obołończyk, Łukasz

2011-01-01

Retroperitoneal fibrosis or Ormond’s disease is an uncommon process characterized by fibrous tissue proliferation in the retroperitoneum, usually involving the aorta, inferior vena cava and iliac vessels. Obstructive hydronephrosis is often observed due to ureteral entrapment. This report presents a case of the peripancreatic location of the disease. The role of CT and MRI in establishing diagnosis of retroperitoneal fibrosis in an atypical site is discussed. A 52-year-old woman with Hashimoto’s thyroiditis was admitted to hospital because of pain suggesting renal colic. The patient was subjected to ultrasound, CT, and MRI which did not confirm urolithiasis but revealed pancreatic infiltration. Partial pancreatectomy, left-sided adrenalectomy and splenectomy were performed. Retroperitoneal fibrosis was diagnosed in the histopathological examination. A few weeks after surgery, a complication such as pancreatitis developed. Repeat CT confirmed it and showed right hydronephrosis secondary to ureteral involvement by a mass adjacent to the common iliac artery (defined as a typical manifestation of retroperitoneal fibrosis). Nephrostomy and conservative treatment improved the clinical state of the patient. No progression of the process was observed in the follow-up examinations. Atypical retroperitoneal fibrosis remains a diagnostic challenge. Imaging techniques CT and MRI are useful tools for evaluating the extent of Ormond’s disease. An unusual distribution of the process (e.g. peripancreatic location reported in this study) requires histopathological assessment to establish the final diagnosis

The PAPAS index: a novel index for the prediction of hepatitis C-related fibrosis.

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Ozel, Banu D; Poyrazoğlu, Orhan K; Karaman, Ahmet; Karaman, Hatice; Altinkaya, Engin; Sevinç, Eylem; Zararsiz, Gökmen

2015-08-01

Several noninvasive tests have been developed to determine the degree of hepatic fibrosis in patients with chronic hepatitis C (CHC) without performing liver biopsy. This study aimed to determine the performance of the PAPAS (Platelet/Age/Phosphatase/AFP/AST) index in patients with CHC for the prediction of significant fibrosis and cirrhosis and to compare it with other noninvasive tests. To date, no study has evaluated the application of the PAPAS index in CHC-associated liver fibrosis. This retrospective study included 137 consecutive patients with CHC who had undergone a percutaneous liver biopsy before treatment. The aspartate aminotransferase/platelet ratio (APRI), aspartate aminotransferase/alanine transaminase ratio (AAR), age-platelet index (API), FIB4, cirrhosis discriminate score (CDS), the Göteborg University cirrhosis index (GUCI), and PAPAS were calculated and compared with the diagnostic accuracies of all fibrosis indices between the groups F0-F2 (no-mild fibrosis) versus F3-F6 (significant fibrosis) and F0-F4 (no cirrhosis) versus F5-F6 (cirrhosis). To predict significant fibrosis, the area under curve (95% confidence interval) for FIB4 was 0.727 followed by GUCI (0.721), PAPAS≈APRI≈CDS (0.716), and API (0.68). To predict cirrhosis, the area under curve (95% confidence interval) for FIB4 was calculated to be 0.735, followed by GUCI (0.723), PAPAS≈APRI≈CDS≈(0.71), and API (0.66). No statistically significant difference was observed among these predictors to exclude both significant fibrosis and cirrhosis (P>0.05). The diagnostic capability of the PAPAS index has moderate efficiency and was not superior to other fibrosis markers for the identification of fibrosis in CHC patients. There is a need for more comprehensive prospective studies to help determine the diagnostic value of PAPAS for liver fibrosis.

Ageing influence for the evaluation of DXA precision in female subjects

International Nuclear Information System (INIS)

Lin Qiang; Yu Wei; Qin Mingwei; Shang Wei; Tian Junping; Han Shaomei

2006-01-01

Objective: To investigate whether aging factor influence the precision of DXA measurement at the lumbar spine in females. Methods: A total of 90 female subjects were recruited and divided into three age groups, i.e. 45-55 years, 56-65 years and 66-75 years. There were 30 female subjects for each age group. Each subject was scanned twice at the same day. Mean BMD values from L2 to L4 were collected and grouped by calculating the root mean square (RMS). Precision errors were expressed as root mean square (RMS). P 2 , (0.992±0.010) g/cm 2 , (0.910±0.010) g/cm 2 , respectively. Mean BMD values from L2 to L4 decreased with increasing age group. Root mean square was lower in the 45 -55 age group, and was same between 56-65 and 66-75 age group. There were significant difference of BMD standard deviation between both there groups (F=5.213, P<0.05) any age group (q value I vs II 0.035; II vs III 0.500; I vs III 0.035, P<0.05). Conclusion: Age could influence the precision of DXA measurement at the site of lumbar spine in females. Therefore, caution should be paid to the age of female subjects recruited for the evaluation of precision for DXA measurement in the clinical trials. (authors)

Complementary and alternative medicine use in children with cystic fibrosis.

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

2016-11-01

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

The role of anaerobic bacteria in the cystic fibrosis airway.

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Sherrard, Laura J; Bell, Scott C; Tunney, Michael M

2016-11-01

Anaerobic bacteria are not only normal commensals, but are also considered opportunistic pathogens and have been identified as persistent members of the lower airway community in people with cystic fibrosis of all ages and stages of disease. Currently, the role of anaerobic bacteria in cystic fibrosis lower airway disease is not well understood. Therefore, this review describes the recent studies relating to the potential pathophysiological role(s) of anaerobes within the cystic fibrosis lungs. The most frequently identified anaerobic bacteria in the lower airways are common to both cystic fibrosis and healthy lungs. Studies have shown that in cystic fibrosis, the relative abundance of anaerobes fluctuates in the lower airways with reduced lung function and increased inflammation associated with a decreased anaerobic load. However, anaerobes found within the lower airways also produce virulence factors, may cause a host inflammatory response and interact synergistically with recognized pathogens. Anaerobic bacteria are potentially members of the airway microbiota in health but could also contribute to the pathogenesis of lower airway disease in cystic fibrosis via both direct and indirect mechanisms. A personalized treatment strategy that maintains a normal microbial community may be possible in the future.

The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis

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Kim, Seok-Jo; Cheresh, Paul; Jablonski, Renea P.; Williams, David B.; Kamp, David W.

2015-01-01

Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis. We focus on the emerging role for AEC mtDNA damage repair by 8-oxoguanine DNA glycosylase (OGG1) and mitochondrial aconitase (ACO-2) in maintaining mtDNA integrity which is important in preventing AEC apoptosis and asbestos-induced pulmonary fibrosis in a murine model. We then review recent studies linking the sirtuin (SIRT) family members, especially SIRT3, to mitochondrial integrity and mtDNA damage repair and aging. We present a conceptual model of how SIRTs modulate reactive oxygen species (ROS)-driven mitochondrial metabolism that may be important for their tumor suppressor function. The emerging insights into the pathobiology underlying AEC mtDNA damage and apoptosis is suggesting novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer. PMID:26370974

Routine blood tests to predict liver fibrosis in chronic hepatitis C.

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Hsieh, Yung-Yu; Tung, Shui-Yi; Lee, Kamfai; Wu, Cheng-Shyong; Wei, Kuo-Liang; Shen, Chien-Heng; Chang, Te-Sheng; Lin, Yi-Hsiung

2012-02-28

To verify the usefulness of FibroQ for predicting fibrosis in patients with chronic hepatitis C, compared with other noninvasive tests. This retrospective cohort study included 237 consecutive patients with chronic hepatitis C who had undergone percutaneous liver biopsy before treatment. FibroQ, aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), AST to platelet ratio index, cirrhosis discriminant score, age-platelet index (API), Pohl score, FIB-4 index, and Lok's model were calculated and compared. FibroQ, FIB-4, AAR, API and Lok's model results increased significantly as fibrosis advanced (analysis of variance test: P fibrosis score in chronic hepatitis C compared with other noninvasive tests. FibroQ is a simple and useful test for predicting significant fibrosis in patients with chronic hepatitis C.

PEDICLE TONGUE FLAP SURGERY IN ORAL SUBMUCOUS FIBROSIS

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Muthubabu K

2016-09-01

Full Text Available BACKGROUND Oral submucous fibrosis is a disease of unknown aetiology and is a legacy of Indians. It has been variously treated both medically and surgically but neither has been found to be rewarding. Various groups have been studying the therapy schedules and aetiological association, but the conclusions have remained unclear. AIM The study aims to focus on newer surgical therapy stressing on the mechanics and use of pedicle tongue flap in the management of this condition. METHODS AND MATERIALS The study comprised of 40 patients from our outpatient department suffering from oral submucous fibrosis in the age group of 11 to 70 years. The contributory factors of oral submucous fibrosis and the symptoms of the disease were evaluated and the role of pedicle tongue flap surgery in the management of this disease which is a premalignant condition is discussed. RESULTS AND CONCLUSION Pedicle tongue flap surgery has given promising results in the treatment of trismus due to oral submucous fibrosis. After the surgery, none of our patients developed any malignant change.

Cystic Fibrosis (CF): Chloride Sweat Test

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... 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 ...

[Age-related changes of sensory peripheral nerve system in healthy subjects.

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Voitenkov, V B; Ekusheva, E V; Komancev, V N; Skripchenko, N V; Grigoryev, S G; Klimkin, A V; Aksenova, A I

2017-01-01

Our aim was to present and evaluate age-related changes of peripheral nerves of limbs on a huge population of healthy subjects of different ages. In 2009-2016 subjects aged from 1months to 90 years were studied by nerve conduction velocity studies (NCV). Data of those confirmed healthy was included in our study. In total there were 372 healthy subjects. NCV for nn. Medianus et Ulnaris was registered, with NCV and amplitude of compound sensory action potential (CSAP) being analyzed. There were significant differences on both these parameters between different age groups. Since the childhood the improvement of conduction (which was reflected in rising of CSAP amplitudes and NCV quickening) was registered; from 40-50 years steady decline of both these parameters were observed in both nerves. Conduction studies of peripheral nerves may be implemented in gerontology for early detection of neurophysiology patterns reflecting physiological aging. Also our results may be implemented for accelerated aging detection.

Prospective validation of FibroTest in comparison with liver stiffness for predicting liver fibrosis in Asian subjects with chronic hepatitis B.

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Beom Kyung Kim

Full Text Available Diagnostic values of FibroTest (FT for hepatic fibrosis have rarely been assessed in Asian chronic hepatitis B (CHB patients. We aimed to validate its diagnostic performances in comparison with liver stiffness (LS.From 2008 to 2010, 194 CHB patients who underwent liver biopsies along with FT and transient elastography were prospectively enrolled. Fibrosis stage was assessed according to the Batts and Ludwig system.To predict significant fibrosis (F≥2, advanced fibrosis (F≥3, and cirrhosis (F = 4, areas under receiver operating characteristic curves (AUROCs of FT were 0.903, 0.907, and 0.866, comparable to those of LS (0.873, 0.897, and 0.910, respectively. Optimized cutoffs of FT to maximize sum of sensitivity and specificity were 0.32, 0.52, and 0.68 for F≥2, F≥3, and F = 4, while those of LS were 8.8, 10.2, and 14.1 kPa, respectively. According to FT and LS cutoffs, 123 (63.4% and 124 (63.9% patients were correctly classified consistent with histological fibrosis (F1, F2, F3, and F4, respectively. Overall concordance between each fibrosis stage estimated by FT and LS was observed in 111 patients, where 88 were correctly classified with histological results. A combination formula adding LS to FT (LS+FT showed similar AUROC levels (0.885, 0.905, and 0.915, while another multiplying LS by FT (LS×FT showed the best AUROCs (0.941, 0.931, and 0.929 for F≥2, F≥3, and F4, respectively.FT provides good fibrosis prediction, with comparable outcomes to LS in Asian CHB patients. FT substantially reduces need for liver biopsy, especially when used in combination with LS.

Subjective physical and cognitive age among community-dwelling older people aged 75 years and older: differences with chronological age and its associated factors.

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Ihira, Hikaru; Furuna, Taketo; Mizumoto, Atsushi; Makino, Keitaro; Saitoh, Shigeyuki; Ohnishi, Hirofumi; Shimada, Hiroyuki; Makizako, Hyuma

2015-01-01

The aim of this cross-sectional study was to determine the associations between self-reported subjective physical and cognitive age, and actual physical and cognitive functions among community-dwelling older people aged 75 years and older. The sample comprised 275 older adults aged 75-91 years. Two questions were asked regarding subjective age: 'How old do you feel physically?' and 'How old do you feel cognitively?' To assess physical functions, we measured handgrip strength, knee extension strength, standing balance and walking speed. Tests of attention, executive function, processing speed and memory were performed to assess actual cognitive function. Subjective physical and cognitive age was associated with performance on all of the physical and cognitive tests, respectively (p older adults who reported themselves as feeling older than their chronological age had a slower walking speed and lower scores for word-list memory recall than those who did not report themselves as feeling older than their actual age. These findings suggest that promoting a fast walking speed and good memory function may help to maintain a younger subjective physical and cognitive age in older adults aged 75 years and older.

The Use of Home Spirometry in Pediatric Cystic Fibrosis Patients

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Aarti Shakkottai MD

2017-02-01

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

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study.

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Kilduff, Claire E; Counter, Melanie J; Thomas, Gareth A; Harrison, Nicholas K; Hope-Gill, Benjamin D

2014-01-01

Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use

Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting Future Lung Function Decline.

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Salisbury, Margaret L; Xia, Meng; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Brown, Kevin K; Wells, Athol U; Schmidt, Shelley L; Martinez, Fernando J; Flaherty, Kevin R

2016-02-01

Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage. Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage. Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Epidemiological evaluation regarding the role of cystic fibrosis as a risk factor for child malnutrition.

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Florescu, Laura; Paduraru, Dana Teodora Anton; Mîndru, Dana Elena; Temneanu, Oana Raluea; Petrariu, F D; Matei, Mioara Calipsoana

2014-01-01

Cystic fibrosis (CF) is the most common monogenic autosomal recessive disorder with progressive chronic evolution which is potentially lethal. Poor growth is a characteristic of children suffering from cystic fibrosis. A poor nutritional status is an independent risk factor for inadequate survival in cystic fibrosis and is associated with disease complications. The appropriate nutritional management is an important part of the treatment so that the patient with cystic fibrosis can achieve normal growth and development and maintain the best possible health status. A balanced diet supplemented with snacks high in fat and calories is necessary to increase the caloric intake in children with cystic fibrosis. Children with cystic fibrosis have higher caloric needs than healthy children of the same age and sex. Malnutrition in CF is multifactorial. Cystic fibrosis is a complex multisystem disorder affecting mainly the gastrointestinal tract and respiratory system. In the past, malnutrition was an inevitable consequence of disease progression, leading to poor growth, impaired respiratory muscle function, decreased exercise tolerance and immunological impairment. A positive association between body weight and height and survival has been widely reported. The energy requirements of patients with CF vary widely and generally increase with age and disease severity. Cystic fibrosis remains a paediatric disorder which is often underdiagnosed but which, if therapeutically managed properly (by means of drug therapy as well as by appropriate physiotherapy techniques), can lead to improved quality of life and, thus, to a bigger life expectancy.

Insights from human genetic studies of lung and organ fibrosis.

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Garcia, Christine Kim

2018-01-02

Genetic investigations of fibrotic diseases, including those of late onset, often yield unanticipated insights into disease pathogenesis. This Review focuses on pathways underlying lung fibrosis that are generalizable to other organs. Herein, we discuss genetic variants subdivided into those that shorten telomeres, activate the DNA damage response, change resident protein expression or function, or affect organelle activity. Genetic studies provide a window into the downstream cascade of maladaptive responses and pathways that lead to tissue fibrosis. In addition, these studies reveal interactions between genetic variants, environmental factors, and age that influence the phenotypic spectrum of disease. The discovery of forces counterbalancing inherited risk alleles identifies potential therapeutic targets, thus providing hope for future prevention or reversal of fibrosis.

Free and protein-bound cobalamin absorption in healthy middle-aged and older subjects.

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van Asselt, D Z; van den Broek, W J; Lamers, C B; Corstens, F H; Hoefnagels, W H

1996-08-01

To study free- and protein-bound cobalamin absorption and the correlation with atrophic gastritis in healthy middle-aged and older subjects. A cross-sectional study. Fifty-two healthy subjects, aged 26 to 87 years, apparently free from conditions known to influence the cobalamin status. Middle-aged subjects were defined as those younger than 65 years of age (median age 57 years) and older subjects as those 65 years and older (median age 75 years). Protein-bound cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of scrambled egg yolk, labeled in vivo with 57 Co-cobalamin by injecting a hen with 57 Co-cyanocobalamin. The percentage of 57 Co-cobalamin bound to protein was 65%. Free cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of crystalline 57 Co-cyanocobalamin. Plasma cobalamin, folate and fasting plasma gastrin, and pepsinogen A and C concentrations were determined. The median urinary excretion of egg yolk 57 Co-cobalamin in middle-aged subjects was 12.3% (25th and 75th percentiles 10.5%-14.5%) compared with 11.7% (25th and 75th percentiles 9.8%-13.6%) in older subjects (P = .283). The median urinary excretion after administration of free 57 Co-cobalamin in middle-aged subjects was 25.7% (25th and 75th percentiles 20.6%-30.7%) compared with 27.9% (25th and 75th percentiles 21.4%-34.5%) in older subjects (P = .694). Neither egg yolk nor free 57 Co-cobalamin excretion correlated with age. A ratio of pepsinogen A to pepsinogen C less than 1.6, indicating atrophic gastritis, was found in 13 subjects. Within the atrophic gastritis group, 11 subjects had a pepsinogen A concentration greater than or equal to 17 micrograms/L, indicating mild to moderate atrophic gastritis, and two subjects had a pepsinogen A concentration less than 17 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. All subjects had normal fasting plasma gastrin concentrations. Free

Adjustment to Aging, Subjective Age and Age Representation: Assessing a Nationally-Diverse Population of Older Adults

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Sofia von Humboldt

2012-11-01

Full Text Available Aim: This research sought to analyse older adults’ conceptualization of adjustment to aging (AtA, subjective age (SA and age representation (AR, adding a cross-national comparative perspective to aging well. Method: Questionnaires were completed, assessing participants’ background information. Semi-structured interviews were performed, addressing three core areas: SA, AtA and AR. Complete information on 231 older adults aged between 74-102 years (M = 83.1; SD = 6.692 from four different nationalities, was available. Data was subjected to content analysis. Results: Seven categories were identified to contribute to AtA: ‘accomplishment, personal fulfilment and future projects’, ‘occupation, profession, autonomy and leisure’, ‘health status, physical and intellectual functioning’, ‘valorisation of time and age’, ‘family, social and interpersonal attachment’, ‘stability, quality and financial situation’, and ‘sense of limit and existential issues’. Five categories were identified for SA: ‘with congruence’, ‘without concern’, ‘with apprehension’, ‘young-at-heart’ and ‘good enough’. For AR, eight emergent categories were found: ‘future investment’, ‘reconciliation with life’, ‘present challenge’, ‘regret about the past’, ‘dynamic life’, ‘with contentment’, ‘as an opportunity’ and ‘with dissatisfaction’. Conclusion: This research contributes for a better understanding of what defines AtA, SA and AR in older adults. Moreover, interventions and communication approaches in clinical practice and program development in health care context should focus on shared perceptions of aging well.

Genetic modifiers of nutritional status in cystic fibrosis.

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Bradley, Gia M; Blackman, Scott M; Watson, Christopher P; Doshi, Vishal K; Cutting, Garry R

2012-12-01

Improved nutrition early in life is associated with better pulmonary function for patients with cystic fibrosis (CF). However, nutritional status is poorly correlated with the CFTR genotype. We investigated the extent to which modifier genes influence nutrition in children with CF. BMI data were longitudinally collected from the CF Twin-Sibling Study and Cystic Fibrosis Foundation Patient Registry for twins and siblings from 2000 to 2010. A nutritional phenotype was derived for 1124 subjects by calculating the average BMI z score from 5-10 y of age (BMI-z(5to10)). The genetic contribution to the variation in BMI-z(5to10) (ie, heritability) was estimated by comparing the similarity of the phenotype in monozygous twins to that in dizygous twins and siblings. Linkage analysis identified potential modifier-gene loci. The median BMI-z(5to10) was -0.07 (range: -3.89 to 2.30), which corresponded to the 47th CDC percentile. BMI-z(5to10) was negatively correlated with pancreatic insufficiency, history of meconium ileus, and female sex but positively correlated with later birth cohorts and lung function. Monozygous twins showed greater concordance for BMI-z(5to10) than did dizygous twins and siblings; heritability estimates from same-sex twin-only analyses ranged from 0.54 to 0.82. For 1010 subjects with pancreatic insufficiency, genome-wide significant linkage was identified on chromosomes 1p36.1 [log of odds (LOD): 5.3] and 5q14 (LOD: 5.1). These loci explained ≥16% and ≥15%, respectively, of the BMI variance. The analysis of twins and siblings with CF indicates a prominent role for genes other than CFTR to BMI variation. Specifically, regions on chromosomes 1 and 5 appear to harbor genetic modifiers of substantial effect.

[Endocrine complications of cystic fibrosis in childhood].

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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.

Mounier-Kuhn Syndrome in an Elderly Female with Pulmonary Fibrosis

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Panagiotis Boglou

2016-01-01

Full Text Available Mounier-Kuhn syndrome (MKS, or tracheobronchomegaly, is a rare clinical and radiologic condition characterized by pronounced tracheobronchial dilation and recurrent lower respiratory tract infections. Tracheobronchomegaly presents when the defect extends to the central bronchi. MKS can be diagnosed in adult women when the transverse and sagittal diameters of the trachea, right mainstem bronchus, and left mainstem bronchus exceed 21, 23, 19.8, and 17.4 mm, respectively. Its diagnosis is based on chest radiograph and chest computed tomography (CT. Patients, usually middle-aged men, may be asymptomatic or present with clinical manifestations ranging from minimal symptoms with preserved lung function to severe respiratory failure. Pulmonary function tests (PFTs typically reveal a restrictive pattern. This report presents an elderly woman with previously diagnosed pulmonary fibrosis with symptoms of increased sputum production and haemoptysis. High-resolution chest CT showed tracheal and main stem bronchi dilatation along with bronchial diverticulosis. PFTs indicated a restrictive pattern characteristic of the underlying pulmonary fibrosis. The patient is the oldest, referred to the female gender, at presentation of MKS hitherto reported. This case highlights the need to include MKS in the differential diagnosis of recurrent lower respiratory tract infections, even in older subjects.

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

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Yasser E Nassef

2013-11-01

Full Text Available The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV paediatric patients (8-14 years were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, hyaluronic acid (HA, procollagen type III amino-terminal peptide (PIIINP and osteopontin (OPN, were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05. The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

Na and K dependence of the Na/K pump in cystic fibrosis fibroblasts.

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Reznik, V M; Schneider, J A; Mendoza, S A

1981-01-01

The Na and K dependence of the Na/K pump was measured in skin fibroblasts from patients with cystic fibrosis and age/sex-matched controls. Under basal conditions, there was no difference between control and cystic fibrosis cells in protein per cell, intracellular Na and K content, or Na/K pump activity (measured as ouabain-sensitive 86Rb uptake). There was no difference in the Na dependence of the Na/K pump between cystic fibrosis cells and control cells. In cells from patients with cystic fi...

Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.

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Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K

2018-02-27

Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases

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

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

Subjective Age Bias: A Motivational and Information Processing Approach

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Teuscher, Ursina

2009-01-01

There is broad empirical evidence, but still a lack of theoretical explanations, for the phenomenon that most older people feel considerably younger than their real age. In this article, a measurement model of subjective age was assessed, and two independent theoretical approaches are proposed: (1) a motivational approach assuming that the age…

Shear Wave Elastography--A New Quantitative Assessment of Post-Irradiation Neck Fibrosis.

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Liu, K H; Bhatia, K; Chu, W; He, L T; Leung, S F; Ahuja, A T

2015-08-01

Shear wave elastography (SWE) is a new technique which provides quantitative assessment of soft tissue stiffness. The aim of this study was to assess the reliability of SWE stiffness measurements and its usefulness in evaluating post-irradiation neck fibrosis. 50 subjects (25 patients with previous radiotherapy to the neck and 25 sex and age-matched controls) were recruited for comparison of SWE stiffness measurements (Aixplorer, Supersonic Imagine). 30 subjects (16 healthy individuals and 14 post-irradiated patients) were recruited for a reliability study of SWE stiffness measurements. SWE stiffness measurements of the sternocleidomastoid muscle and the overlying subcutaneous tissues of the neck were made. The cross-sectional area and thickness of the sternocleidomastoid muscle and the overlying subcutaneous tissue thickness of the neck were also measured. The post-irradiation duration of the patients was recorded. The intraclass correlation coefficients for the intraoperator and interoperator reliability of deep and subcutaneous tissue SWE stiffness ranged from 0.90-0.99 and 0.77-0.94, respectively. The SWE stiffness measurements (mean +/- SD) of deep and subcutaneous tissues were significantly higher in the post-irradiated patients (64.6 ± 46.8 kPa and 63.9 ± 53.1 kPa, respectively) than the sex and age-matched controls (19.9 ± 7.8 kPa and 15.3 ± 8.37 respectively) (p < 0.001). The SWE stiffness increased with increasing post-irradiation therapy duration in the Kruskal Wallis test (p < 0.001) and correlated with muscle atrophy and subcutaneous tissue thinning (p < 0.01). SWE is a reliable technique and may potentially be an objective and specific tool in quantifying deep and subcutaneous tissue stiffness, which in turn reflects the severity of neck fibrosis. © Georg Thieme Verlag KG Stuttgart · New York.

Stress and Subjective Age: Those With Greater Financial Stress Look Older.

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Agrigoroaei, Stefan; Lee-Attardo, Angela; Lachman, Margie E

2017-12-01

Subjective indicators of age add to our understanding of the aging process beyond the role of chronological age. We examined whether financial stress contributes to subjective age as rated by others and the self. The participants ( N = 228), aged 26-75, were from a Boston area satellite of the Midlife in the United States (MIDUS) longitudinal study. Participants reported how old they felt and how old they thought they looked, and observers assessed the participants' age based on photographs (other-look age), at two occasions, an average of 10 years apart. Financial stress was measured at Time 1. Controlling for income, general stress, health, and attractiveness, participants who reported higher levels of financial stress were perceived as older than their actual age to a greater extent and showed larger increases in other-look age over time. We consider the results on accelerated aging of appearance with regard to their implications for interpersonal interactions and in relation to health.

Non-invasive assessment of exercise performance in children with cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis: is there a CF specific muscle defect?

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Rosenthal, Mark; Narang, Indra; Edwards, Liz; Bush, Andrew

2009-03-01

Peripheral muscle dysfunction is increasingly recognized as complicating respiratory disease, but this is difficult to measure non-invasively. Can skeletal muscle function and efficiency be measured during exercise non-invasively using respiratory mass spectrometry (RMS); and is the known exercise dysfunction in cystic fibrosis (CF) children related in part to a disease specific defect of skeletal muscle, or a non-specific manifestation of chronic airway infection and inflammation. Calculations of effective pulmonary blood flow and stroke volume, blood oxygen content and oxygen dispatch from the lungs, skeletal muscle oxygen extraction and consumption, anerobic threshold and capacity, and gross, net and work efficiency in 106 controls and 36 children (18 CF) with bronchiectasis, all aged from 8 to 17 years. Normal values for control subjects are tabulated. CF and non-CF bronchiectatic subjects had similar physiology, and skeletal muscle abnormalities could not be detected. Reduced oxygen dispatch from the lungs, due to an inability to raise stroke volume, without an increase in functional residual capacity was the major factor in reduced exercise ability. Non-invasive RMS can be used to determine skeletal muscle function in children. The changes observed in CF subjects were very similar to non-CF bronchiectatic subjects and thus a CF specific defect was not demonstrated.

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

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

2010-06-01

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

TINF2 Gene Mutation in a Patient with Pulmonary Fibrosis

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T. W. Hoffman

2016-01-01

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

A neglected problem of developing countries: Noncystic fibrosis bronchiectasis

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Babayigit, Arzu; Olmez Duygu; Uzuner Nevin; Cakmakci, Handan; Tuncel Tuba; Karaman Ozkan

2009-01-01

Bronchiectasis has been defined as the abnormal and permanent dilation of the bronchi. It is still an important problem in many developing countries. The aim of this study was to identify the chacteristics and underlying etiology of children followed with the diagnosis of noncystic fibrosis bronchiectasis. Children with bronchiectasis confirmed with high-resolution computed tomography were enrolled into the study. The data of the patients, including symptoms of the disease, age at the onset of symptoms, findings of physical examination, labrotory investigations performed in order to identify the etiology of bronchiectasis, etiology of bronchiectasis if found, radiologic findings and treatment modalities were noted. Sixty-six children between 1 and 17 years were included in the study retrospectively. Forty-four of them were males (66.7%) and 22 (33.3%) were females. The most common presenting symptoms were cough (100%) and sputum expectoration (50%). An underlying etiology was identified in 44 (66.7%) of the study subjects. The four most common underlying causes were found as infections (21.2%), asthma (16.7%), aspiration syndromes and/or gastroesophageal reflux disease (9.1%) and immunodeficiency syndromes (7.6%), respectively. Identifying an underlying etiology will have a significant effect on the management of noncystic fibrosis bronchiectasis. Defining the cause of bronchiectasis may also decrease its incidence, progression and complications. (author)

Subjective Technology Adaptivity Predicts Technology Use in Old Age.

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Kamin, Stefan T; Lang, Frieder R; Beyer, Anja

2017-01-01

To date, not much is known about the psychological and motivational factors underlying technology use in late life. What are the interindividual determinants that lead older adults to invest in using technological innovations despite the age-related physiological changes that impose challenges on behavioral plasticity in everyday life? This research explores interindividual differences in subjective technology adaptivity - a general technology-related motivational resource that accounts for technology use in late life. More specifically, we investigate the influence of this factor relative to demographic characteristics, personality traits, and functional limitations in a longitudinal sample of community-dwelling older adults. We report results from a paper-and-pencil survey with 136 older adults between 59 and 92 years of age (mean = 71.4, SD = 7.4). Of those participants, 77 participated in a 2-year follow-up. We assessed self-reports of technology use, subjective technology adaptivity, functional limitations, and the personality traits openness to new experiences and neuroticism. Higher levels of subjective technology adaptivity were associated with technology use at the first measurement as well as increased use over the course of 2 years. Subjective technology adaptivity is a significant predictor of technology use in old age. Our findings contribute to improving the understanding of interindividual differences when using technological innovation in late life. Moreover, our findings have implications in the context of user involvement and may contribute to the successful development of innovative technology for older adults. © 2017 S. Karger AG, Basel.

Computer-assisted analysis of cervical vertebral bone age using cephalometric radiographs in Brazilian subjects.

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Caldas, Maria de Paula; Ambrosano, Gláucia Maria Bovi; Haiter Neto, Francisco

2010-01-01

The aims of this study were to develop a computerized program for objectively evaluating skeletal maturation on cephalometric radiographs, and to apply the new method to Brazilian subjects. The samples were taken from the patient files of Oral Radiological Clinics from the North, Northeast, Midwest and South regions of the country. A total of 717 subjects aged 7.0 to 15.9 years who had lateral cephalometric radiographs and hand-wrist radiographs were selected. A cervical vertebral computerized analysis was created in the Radiocef Studio 2 computer software for digital cephalometric analysis, and cervical vertebral bone age was calculated using the formulas developed by Caldas et al.17 (2007). Hand-wrist bone age was evaluated by the TW3 method. Analysis of variance (ANOVA) and the Tukey test were used to compare cervical vertebral bone age, hand-wrist bone age and chronological age (P cervical vertebral bone age and chronological age in all regions studied. When analyzing bone age, it was possible to observe a statistically significant difference between cervical vertebral bone age and hand-wrist bone age for female and male subjects in the North and Northeast regions, as well as for male subjects in the Midwest region. No significant difference was observed between bone age and chronological age in all regions except for male subjects in the North and female subjects in the Northeast. Using cervical vertebral bone age, it might be possible to evaluate skeletal maturation in an objective manner using cephalometric radiographs.

Context influences on the relationship between views of aging and subjective age: The moderating role of culture and domain of functioning.

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Hess, Thomas M; O'Brien, Erica L; Voss, Peggy; Kornadt, Anna E; Rothermund, Klaus; Fung, Helene H; Popham, Lauren E

2017-08-01

Subjective age has been shown to reliably predict a variety of psychological and physical health outcomes, yet our understanding of its determinants is still quite limited. Using data from the Aging as Future project, the authors examined the degree to which views of aging influence subjective age and how this influence varies across cultures and domains of everyday functioning. Using data from 1,877 adults aged from 30 to 95 years of age collected in China, Germany, and the United States, they assessed how general attitudes about aging and perceptions of oneself as an older adult influenced subjective age estimates in 8 different domains of functioning. More positive attitudes about aging were associated with older subjective ages, whereas more positive views of self in old age were associated with younger subjective age. It is hypothesized that these effects are reflective of social-comparison processes and self-protective mechanisms. These influences varied considerably over contexts, with views of aging having a greater impact in domains associated with stronger negative stereotypes of aging (e.g., health) compared to those with more positive ones (e.g., family). Culture also moderated the impact of aging views in terms of the strength of prediction, direction of effect, and age of greatest influence, presumably due to cultural differences in the salience and strength of aging-related belief systems across contexts. The results illustrate the contextual sensitivity of subjective age and highlight the role played by an individual's views of old age-both in general and regarding oneself-in determining their own experience of aging. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Management of suspected monogenic lung fibrosis in a specialised centre

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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.

Age, subjective stress, and depression after ischemic stroke.

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McCarthy, Michael J; Sucharew, Heidi J; Alwell, Kathleen; Moomaw, Charles J; Woo, Daniel; Flaherty, Matthew L; Khatri, Pooja; Ferioli, Simona; Adeoye, Opeolu; Kleindorfer, Dawn O; Kissela, Brett M

2016-02-01

The incidence of stroke among younger adults in the United States is increasing. Few studies have investigated the prevalence of depressive symptoms after stroke among different age groups or the extent to which subjective stress at the time of stroke interacts with age to contribute to post-stroke depression. The present study examined whether there exists an age gradient in survivors' level of depressive symptoms and explored the extent to which financial, family, and health-related stress may also impact on depression. Bivariate analyses (N = 322) indicated significant differences in depression and stress by age group, as well as differences in age and stress by 3-month depression status. Linear regression analyses indicated that survivors between the ages of 25-54 and 55-64 years old had, on average, significantly higher depressive symptom scores. Those with financial, family, and health-related stress at the time of stroke, irrespective of age, also had significantly higher scores.

A new model using routinely available clinical parameters to predict significant liver fibrosis in chronic hepatitis B.

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Wai-Kay Seto

Full Text Available OBJECTIVE: We developed a predictive model for significant fibrosis in chronic hepatitis B (CHB based on routinely available clinical parameters. METHODS: 237 treatment-naïve CHB patients [58.4% hepatitis B e antigen (HBeAg-positive] who had undergone liver biopsy were randomly divided into two cohorts: training group (n = 108 and validation group (n = 129. Liver histology was assessed for fibrosis. All common demographics, viral serology, viral load and liver biochemistry were analyzed. RESULTS: Based on 12 available clinical parameters (age, sex, HBeAg status, HBV DNA, platelet, albumin, bilirubin, ALT, AST, ALP, GGT and AFP, a model to predict significant liver fibrosis (Ishak fibrosis score ≥3 was derived using the five best parameters (age, ALP, AST, AFP and platelet. Using the formula log(index+1 = 0.025+0.0031(age+0.1483 log(ALP+0.004 log(AST+0.0908 log(AFP+1-0.028 log(platelet, the PAPAS (Platelet/Age/Phosphatase/AFP/AST index predicts significant fibrosis with an area under the receiving operating characteristics (AUROC curve of 0.776 [0.797 for patients with ALT <2×upper limit of normal (ULN] The negative predictive value to exclude significant fibrosis was 88.4%. This predictive power is superior to other non-invasive models using common parameters, including the AST/platelet/GGT/AFP (APGA index, AST/platelet ratio index (APRI, and the FIB-4 index (AUROC of 0.757, 0.708 and 0.723 respectively. Using the PAPAS index, 67.5% of liver biopsies for patients being considered for treatment with ALT <2×ULN could be avoided. CONCLUSION: The PAPAS index can predict and exclude significant fibrosis, and may reduce the need for liver biopsy in CHB patients.

Epidemiology of idiopathic pulmonary fibrosis

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Ley B

2013-11-01

Full Text Available Brett Ley, Harold R Collard Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, USA Abstract: Idiopathic pulmonary fibrosis is a chronic fibrotic lung disease of unknown cause that occurs in adults and has a poor prognosis. Its epidemiology has been difficult to study because of its rarity and evolution in diagnostic and coding practices. Though uncommon, it is likely underappreciated both in terms of its occurrence (ie, incidence, prevalence and public health impact (ie, health care costs and resource utilization. Incidence and mortality appear to be on the rise, and prevalence is expected to increase with the aging population. Potential risk factors include occupational and environmental exposures, tobacco smoking, gastroesophageal reflux, and genetic factors. An accurate understanding of its epidemiology is important, especially as novel therapies are emerging. Keywords: idiopathic pulmonary fibrosis, epidemiology, incidence, prevalence, mortality, risk factors

Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice

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Wang, Xingqi; Ouyang, Zijun; You, Qian; He, Shuai; Meng, Qianqian; Hu, Chunhui; Wu, Xudong; Shen, Yan; Sun, Yang, E-mail: yangsun@nju.edu.cn; Wu, Xuefeng, E-mail: wuxf@nju.edu.cn; Xu, Qiang, E-mail: molpharm@163.com

2016-07-15

Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression of icam1, vcam1, inos and cox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and α-SMA in lung tissues as well as the levels of TGF-β1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-β1-induced epithelial-mesenchymal transition via Smad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis. - Highlights: • Obaculactone ameliorates bleomycin-induced pulmonary fibrosis in mice. • Obaculactone mitigates bleomycin-induced inflammatory response in lungs. • Obaculactone exerts inhibitory effects on TGF-β1 signaling and TGF-β1-induced EMT progress.

Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice

International Nuclear Information System (INIS)

Wang, Xingqi; Ouyang, Zijun; You, Qian; He, Shuai; Meng, Qianqian; Hu, Chunhui; Wu, Xudong; Shen, Yan; Sun, Yang; Wu, Xuefeng; Xu, Qiang

2016-01-01

Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactone inhibited the expression of icam1, vcam1, inos and cox2, and attenuated oxidative stress in bleomycin-treated lungs. Importantly, the production of collagen I and α-SMA in lung tissues as well as the levels of TGF-β1, ALK5, p-Smad2 and p-Smad3 in lung homogenates was also reduced after obaculactone treatment. Finally, the TGF-β1-induced epithelial-mesenchymal transition via Smad-dependent and Smad-independent pathways was reversed by obaculactone. Collectively, these data suggest that obaculactone may be a promising drug candidate for the treatment of idiopathic pulmonary fibrosis. - Highlights: • Obaculactone ameliorates bleomycin-induced pulmonary fibrosis in mice. • Obaculactone mitigates bleomycin-induced inflammatory response in lungs. • Obaculactone exerts inhibitory effects on TGF-β1 signaling and TGF-β1-induced EMT progress.

Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa.

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Klepac-Ceraj, Vanja; Lemon, Katherine P; Martin, Thomas R; Allgaier, Martin; Kembel, Steven W; Knapp, Alixandra A; Lory, Stephen; Brodie, Eoin L; Lynch, Susan V; Bohannan, Brendan J M; Green, Jessica L; Maurer, Brian A; Kolter, Roberto

2010-05-01

Polymicrobial bronchopulmonary infections in cystic fibrosis (CF) cause progressive lung damage and death. Although the arrival of Pseudomonas aeruginosa often heralds a more rapid rate of pulmonary decline, there is significant inter-individual variation in the rate of decline, the causes of which remain poorly understood. By coupling culture-independent methods with ecological analyses, we discovered correlations between bacterial community profiles and clinical disease markers in respiratory tracts of 45 children with CF. Bacterial community complexity was inversely correlated with patient age, presence of P. aeruginosa and antibiotic exposure, and was related to CF genotype. Strikingly, bacterial communities lacking P. aeruginosa were much more similar to each other than were those containing P. aeruginosa, regardless of antibiotic exposure. This suggests that community composition might be a better predictor of disease progression than the presence of P. aeruginosa alone and deserves further study.

Feeling sad makes us feel older: Effects of a sad-mood induction on subjective age.

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Dutt, Anne J; Wahl, Hans-Werner

2017-08-01

A mood-induction paradigm was implemented in a sample of 144 adults covering midlife and old age (40-80 years) to investigate associations between mood and subjective age. Sad or neutral mood was induced by texts and music pieces. Subjective age was operationalized as felt age relative to chronological age. Participants receiving the sad-mood induction reported changes toward older felt ages from pre- to postinduction. Participants receiving the neutral-mood induction reported comparable levels of subjective age at pre- and postinduction. Effects were comparable across middle- and older aged participants. Results suggest that sad affective states might dampen subjective age. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Computer-assisted analysis of cervical vertebral bone age using cephalometric radiographs in Brazilian subjects

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Maria de Paula Caldas

2010-03-01

Full Text Available The aims of this study were to develop a computerized program for objectively evaluating skeletal maturation on cephalometric radiographs, and to apply the new method to Brazilian subjects. The samples were taken from the patient files of Oral Radiological Clinics from the North, Northeast, Midwest and South regions of the country. A total of 717 subjects aged 7.0 to 15.9 years who had lateral cephalometric radiographs and hand-wrist radiographs were selected. A cervical vertebral computerized analysis was created in the Radiocef Studio 2 computer software for digital cephalometric analysis, and cervical vertebral bone age was calculated using the formulas developed by Caldas et al.17 (2007. Hand-wrist bone age was evaluated by the TW3 method. Analysis of variance (ANOVA and the Tukey test were used to compare cervical vertebral bone age, hand-wrist bone age and chronological age (P < 0.05. No significant difference was found between cervical vertebral bone age and chronological age in all regions studied. When analyzing bone age, it was possible to observe a statistically significant difference between cervical vertebral bone age and hand-wrist bone age for female and male subjects in the North and Northeast regions, as well as for male subjects in the Midwest region. No significant difference was observed between bone age and chronological age in all regions except for male subjects in the North and female subjects in the Northeast. Using cervical vertebral bone age, it might be possible to evaluate skeletal maturation in an objective manner using cephalometric radiographs.

Hyperleptinemia Exacerbates High-Fat Diet-Mediated Atrial Fibrosis and Fibrillation.

Science.gov (United States)

Fukui, Akira; Ikebe-Ebata, Yuki; Kondo, Hidekazu; Saito, Shotaro; Aoki, Kohei; Fukunaga, Naoya; Shinohara, Tetsuji; Masaki, Takayuki; Teshima, Yasushi; Takahashi, Naohiko

2017-06-01

Obesity including metabolic syndrome is an independent risk factor of atrial fibrillation (AF). Although hyperleptinemia is usually a characteristic of obese subjects, the relationship with atrial fibrosis and AF is unknown. We tested the hypothesis that high-fat diet (HFD)-induced hyperleptinemia exacerbates atrial fibrosis and AF. Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob (Ob) mice were treated with a normal-fat diet (NFD) or 60% HFD. After 8 weeks, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed and left atrial (LA) tissues were collected for histological analysis, hydroxyproline assay, and reverse transcription-polymerase chain reaction. HFD treatment increased body weight in both WT and Ob mice compared with NFD (both P atrial fibrosis and AF. Inhibition of leptin signaling may become a novel therapeutic target to prevent obesity-related AF. © 2017 Wiley Periodicals, Inc.

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

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

2015-01-01

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

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

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

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

Genetic modifiers of nutritional status in cystic fibrosis1234

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Bradley, Gia M; Blackman, Scott M; Watson, Christopher P; Doshi, Vishal K; Cutting, Garry R

2012-01-01

Background: Improved nutrition early in life is associated with better pulmonary function for patients with cystic fibrosis (CF). However, nutritional status is poorly correlated with the CFTR genotype. Objective: We investigated the extent to which modifier genes influence nutrition in children with CF. Design: BMI data were longitudinally collected from the CF Twin-Sibling Study and Cystic Fibrosis Foundation Patient Registry for twins and siblings from 2000 to 2010. A nutritional phenotype was derived for 1124 subjects by calculating the average BMI z score from 5–10 y of age (BMI-z5to10). The genetic contribution to the variation in BMI-z5to10 (ie, heritability) was estimated by comparing the similarity of the phenotype in monozygous twins to that in dizygous twins and siblings. Linkage analysis identified potential modifier-gene loci. Results: The median BMI-z5to10 was −0.07 (range: −3.89 to 2.30), which corresponded to the 47th CDC percentile. BMI-z5to10 was negatively correlated with pancreatic insufficiency, history of meconium ileus, and female sex but positively correlated with later birth cohorts and lung function. Monozygous twins showed greater concordance for BMI-z5to10 than did dizygous twins and siblings; heritability estimates from same-sex twin-only analyses ranged from 0.54 to 0.82. For 1010 subjects with pancreatic insufficiency, genome-wide significant linkage was identified on chromosomes 1p36.1 [log of odds (LOD): 5.3] and 5q14 (LOD: 5.1). These loci explained ≥16% and ≥15%, respectively, of the BMI variance. Conclusions: The analysis of twins and siblings with CF indicates a prominent role for genes other than CFTR to BMI variation. Specifically, regions on chromosomes 1 and 5 appear to harbor genetic modifiers of substantial effect. PMID:23134884

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

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

2015-05-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Far-Infrared Radiation Thermotherapy Improves Tissue Fibrosis in Chronic Extremity Lymphedema.

Science.gov (United States)

Li, Ke; Zhang, Zheng; Liu, Ning Fei; Sadigh, Parviz; Evans, Verity Joyce; Zhou, Huihong; Gao, Weiqing; Zhang, Yi Xin

2017-09-29

Fibrosis can enhance the exacerbation of lymphedema, which becomes obvious in late stage II-III lymphedema. However, whether far-infrared radiation thermotherapy (FIRT) can cure lymphedema fibrosis is still lack of research. This research was to investigate the therapeutic effect of FIRT on tissue fibrosis in the treatment of Late stage II-III lymphedema. Patients accepted only FIRT for a total of 20 sessions. The treatment session duration was 2 hours, and a stable machine temperature of 42°C was maintained throughout treatments. Clinical evaluation and laboratory evaluation were conducted before and after FIRT. Clinical outcome measures included circumference of affected extremity, skin elasticity, ultrasound, patients' subjective assessment, and quality of life (QOL). Laboratory outcome measures included serum and local lymphedema tissue fluid concentrations of fibrosis associated cytokines, tissue growth factor beta-1 (TGF-β1), interleukin (IL)-1β, IL-4, IL-18, and caspase-1. Between 2015 and 2016, clinical evaluation of 64 patients with late stage II-III lymphedema was conducted. From this group, 12 cases (18.75%) underwent simultaneous laboratory evaluation. Circumferences of affected extremities improved significantly following treatment (p pain, discomfort, and numbness (p effective treatment for lymphedema tissue fibrosis; it reduces the concentration of fibrosis cytokines in local lymphedema tissues. Consequently, this treatment can reduce the density of fibrosed tissue in the affected extremity, increase skin elasticity, significantly improve clinical symptoms, and improve QOL of patients.

The Combined Effects of Daily Stressors and Major Life Events on Daily Subjective Ages.

Science.gov (United States)

Bellingtier, Jennifer A; Neupert, Shevaun D; Kotter-Grühn, Dana

2017-07-01

Stressors may be a contributing factor in determining how old an individual feels, looks, or would like to be. Currently, little research has been devoted to understanding the relationship between stressors and subjective age in older adults. We focus on the combined impact of major life-event stressors and daily stressors on multiple indicators of subjective age: felt age, ideal age, and look age. Furthermore, we examine the process by which daily stressors relate to subjective ages by testing whether positive affect, control, and negative affect mediate this relationship. Using a daily-diary design, the current study measured older adults' (60-96 years old) stressors, subjective ages, personal control, and affect. Felt, ideal, and look ages each demonstrated a unique pattern of interactions between daily stressors and major life-event stressors. Furthermore, our findings suggest that on the daily level, the relationship between stressors and felt age is mediated by negative affect but not by control and positive affect. Findings indicate the need to consider the broader contextual picture of stressors, as well as their differential impact on multiple indicators of subjective age. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Active Video Game Playing in Children and Adolescents With Cystic Fibrosis: Exercise or Just Fun?

Science.gov (United States)

Salonini, Elena; Gambazza, Simone; Meneghelli, Ilaria; Tridello, Gloria; Sanguanini, Milva; Cazzarolli, Clizia; Zanini, Alessandra; Assael, Baroukh M

2015-08-01

Xbox Kinect has been proposed as an exercise intervention in cystic fibrosis (CF), but its potential has not been compared with standard training modalities. Using a crossover design, subjects were randomized to 2 intervention groups: Xbox Kinect and a traditional stationary cycle. Heart rate, SpO2, dyspnea, and fatigue were measured. Subject satisfaction was tested. Thirty subjects with CF (11 males, mean ± SD age of 12 ± 2.5 y, mean ± SD FEV1 of 73 ± 16% of predicted) were enrolled. Xbox Kinect provided a cardiovascular demand similar to a stationary cycle, although the modality was different (interval vs. continuous). Maximum heart rates were similar (P = .2). Heart rate target was achieved more frequently with a stationary cycle (P = .02). Xbox Kinect caused less dyspnea (P = .001) and fatigue (P < .001) and was more enjoyable than a stationary cycle (P < .001). Subjects preferred Xbox Kinect for its interactivity. Xbox Kinect has the potential to be employed as an exercise intervention in young subjects with CF, but investigation over longer periods is needed. Copyright © 2015 by Daedalus Enterprises.

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

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Costa Luciano Bello

2002-01-01

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

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

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Kalnins D

2012-06-01

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

Suboptimal vitamin K status despite supplementation in children and young adults with cystic fibrosis.

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Dougherty, Kelly A; Schall, Joan I; Stallings, Virginia A

2010-09-01

For children and adolescents with cystic fibrosis (CF) and pancreatic insufficiency, the efficacy of routine vitamin K supplementation to normalize vitamin K status remains unclear. This study examined and determined predictors of vitamin K status in subjects aged 8-25 y with CF and pancreatic insufficiency taking various vitamin K supplements. In 97 subjects, serum 25-hydroxyvitamin D [25(OH)D], dietary intake, vitamin K supplement intake, and vitamin K statusmdashdetermined on the basis of the percentage of serum undercarboxylated osteocalcin (%ucOC; sufficient: lt 20%) and plasma proteins induced by vitamin K absence-factor II (PIVKA-II; n = 60; sufficient: le 2 microg/L)mdashwere assessed. The vitamin K supplementation groups were as follows: lt 150 microg/d (low; multivitamins or no supplement), 150-999 microg/d (middle; CF-specific vitamins), and ge 1000 microg/d (high; mephyton). %ucOC values were compared with 140 healthy subjects aged 6-21 y. In subjects with CF, the median (range) %ucOC was 35% (3%, 76%) and the median (range) for PIVKA-II was 2 (0, 42) micro g/L. Subjects with CF had a higher %ucOC with low [45% (10%, 76%)] and medium [41% (3%, 66%)] supplement intakes but not with a high supplement intake [16% (4%, 72%)] compared with healthy subjects [23% (0%, 43%); both P lt 0.05]. Supplementation group for males and females and 25(OH)D and age for males were significant predictors of vitamin K status. Vitamin K status was often suboptimal despite routine supplementation. Only subjects taking high-dose vitamin K achieved a status similar to healthy subjects, and only the vitamin K supplementation dose predicted vitamin K status for males and females. These data suggest that higher doses of vitamin K are required.

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

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

2013-09-01

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

Pathological assessment of liver fibrosis regression

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WANG Bingqiong

2017-03-01

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

Experimental models of liver fibrosis.

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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.

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

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Serena Schippa

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

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

Science.gov (United States)

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

2013-01-01

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

Influence of age on left ventricular performance during exercise in normal Japanese subject

International Nuclear Information System (INIS)

Konishi, Tokuji; Koyama, Takao; Aoki, Toshikazu; Makino, Katsutoshi; Yamamuro, Masashi; Nakai, Kyudayu; Nakamura, Masayuki; Nakano, Takeshi.

1990-01-01

To assess the effects of age on left ventricular performance, multistage supine ergometer exercise radionuclide ventriculography (RNV) was performed in 92 normal subjects. The subjects ranged in age from 24 to 86 years and were free of cardiopulmonary disease and diabetes. Age-related changes in exercise duration, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), cardiac output (CO) left ventricular ejection fraction (LVEF), left ventricular dv/dt, systolic and diastolic time indexes of dv/dt, and peak systolic pressure/left ventricular end-systolic volume (PSP/LVESV) were analyzed at rest and during the peak exercise stage. Age-related decrease in LVEDV and peak diastolic dv/dt were significant at rest. The time indexes of ECG R to peak systolic dv/dt and time of end-systole to peak diastolic dv/dt also were prolonged with age. Both maximum heart rate and exercise duration were shown to decline with age. No age-related difference was observed in LVESV, LVEF or PSP/LVESV either at rest or during exercise. However, the change of LVEF and LVESV during exercise was less in subjects aged 60 or more. These results indicate decreased left ventricular function during exercise in elderly subjects. (author)

Serial lung function and responsiveness in cystic fibrosis during early childhood

DEFF Research Database (Denmark)

Nielsen, Kim G; Pressler, Tacjana; Klug, Bent

2004-01-01

to bronchodilators and cold air in 30 children (mean [range] age 5.7 [2 to 8] years) with cystic fibrosis (CF). Spirometry was done at school age. Mean sRaw was consistently abnormal: the mean z score (SD) was 2.52 (2.02) (p z score (SD...

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

Deep learning for staging liver fibrosis on CT: a pilot study.

Science.gov (United States)

Yasaka, Koichiro; Akai, Hiroyuki; Kunimatsu, Akira; Abe, Osamu; Kiryu, Shigeru

2018-05-14

To investigate whether liver fibrosis can be staged by deep learning techniques based on CT images. This clinical retrospective study, approved by our institutional review board, included 496 CT examinations of 286 patients who underwent dynamic contrast-enhanced CT for evaluations of the liver and for whom histopathological information regarding liver fibrosis stage was available. The 396 portal phase images with age and sex data of patients (F0/F1/F2/F3/F4 = 113/36/56/66/125) were used for training a deep convolutional neural network (DCNN); the data for the other 100 (F0/F1/F2/F3/F4 = 29/9/14/16/32) were utilised for testing the trained network, with the histopathological fibrosis stage used as reference. To improve robustness, additional images for training data were generated by rotating or parallel shifting the images, or adding Gaussian noise. Supervised training was used to minimise the difference between the liver fibrosis stage and the fibrosis score obtained from deep learning based on CT images (F DLCT score) output by the model. Testing data were input into the trained DCNNs to evaluate their performance. The F DLCT scores showed a significant correlation with liver fibrosis stage (Spearman's correlation coefficient = 0.48, p deep learning model based on CT images, with moderate performance. • Liver fibrosis can be staged by a deep learning model based on magnified CT images including the liver surface, with moderate performance. • Scores from a trained deep learning model showed moderate correlation with histopathological liver fibrosis staging. • Further improvement are necessary before utilisation in clinical settings.

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

DEFF Research Database (Denmark)

Jalal, S; Ciofu, O; Høiby, Niels

2000-01-01

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

Dynamic contrast-enhanced magnetic resonance imaging with Gd-EOB-DTPA for the evaluation of liver fibrosis in chronic hepatitis patients

International Nuclear Information System (INIS)

Chen, Bang-Bin; Hsu, Chao-Yu.; Yu, Chih-Wei; Wei, Shwu-Yuan; Shih, Tiffany Ting-Fang; Kao, Jia-Horng; Lee, Hsuan-Shu

2012-01-01

To develop a non-invasive MRI method for evaluation of liver fibrosis, with histological analysis as the reference standard. The study protocol was approved by the Institutional Review Board for Human Studies of our hospital, and written informed consent was obtained from all subjects. Seventy-nine subjects who received dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA were divided into three subgroups according to Metavir score: no fibrosis (n = 30), mild fibrosis (n = 34), and advanced fibrosis (n = 15). The DCE-MRI parameters were measured using two models: (1) dual-input single-compartment model for arterial blood flow (F a ), portal venous blood flow, total liver blood flow, arterial fraction (ART), distribution volume, and mean transit time; and (2) curve analysis model for Peak, Slope, and AUC. Statistical analysis was performed with Student's t-test and the nonparametric Kruskal-Wallis test. Slope and AUC were two best perfusion parameters to predict the severity of liver fibrosis (>F2 vs. ≤F2). Four significantly different variables were found between non-fibrotic versus mild-fibrotic subgroups: F a , ART, Slope, and AUC; the best predictor for mild fibrosis was F a (AUROC:0.701). DCE-MRI with Gd-EOB-DTPA is a noninvasive imaging, by which multiple perfusion parameters can be measured to evaluate the severity of liver fibrosis. (orig.)

Endocrine Disorders in Cystic Fibrosis.

Science.gov (United States)

Blackman, Scott M; Tangpricha, Vin

2016-08-01

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

"Bong lung" in cystic fibrosis: a case report

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Hauser Jenny

2010-11-01

Full Text Available Abstract Introduction Marijuana or "bong" lung has been recently described. Subjects typically develop large peripheral paraseptal lung bullae and are predisposed to spontaneous pneumothoraces. The underlying mechanism for bullae formation is uncertain, but probably relates to direct lung toxicity and repeated barotrauma as the smoker performs frequent valsalva manoeuvres in an attempt to derive a greater drug effect. Case presentation We describe a case of probable "bong lung" occurring in a 23-year-old Caucasian man with cystic fibrosis who had a history of recurrent pneumothoraces and unusual findings on sputum cytology. Conclusion Our case highlights the importance of questioning young adult cystic fibrosis patients about illicit drug use and the utility of sputum cytology and computed tomography scanning when patients present with pneumothoraces and deteriorations in clinical status.

Dietary copper: a novel predisposing factor for oral submucous fibrosis?

NARCIS (Netherlands)

Arakeri, G.; Brennan, P.A.

2013-01-01

Oral submucous fibrosis (OSMF) is known devastating disorder commonly seen in South Asian developing countries. It is directly linked to areca nut chewing and the contents of areca are subjected to multitude of investigations. Among all the contents of areca nut, the copper element has been

Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

International Nuclear Information System (INIS)

Constantinou, Maria A.; Theocharis, Stamatios E.; Mikros, Emmanuel

2007-01-01

Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using 1 H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. 1 H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA). Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the 1 H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression and could be extended in clinical diagnosis for the management of cirrhotic patients

Diagnosis and quantification of hepatic fibrosis in children with diffusion weighted MR imaging

Energy Technology Data Exchange (ETDEWEB)

Razek, Ahmed Abdel Khalek Abdel, E-mail: arazek@mans.eun.eg [Diagnostic Radiology Department, Mansoura Faculty of Medicine, 62 ElNokrasi Street Meet Hadr, Mansoura 3512 (Egypt); Abdalla, Ahmed [Pediatric Department, Mansoura Faculty of Medicine, Mansoura (Egypt); Omran, Eman [Diagnostic Radiology Department, Mansoura Faculty of Medicine, 62 ElNokrasi Street Meet Hadr, Mansoura 3512 (Egypt); Fathy, Abeer [Pediatric Department, Mansoura Faculty of Medicine, Mansoura (Egypt); Zalata, Khaled [Diagnostic Pathology Department, Mansoura Faculty of Medicine, Mansoura (Egypt)

2011-04-15

Purpose: To evaluate the accuracy of diffusion weighted MR imaging in diagnosis and quantification of hepatic fibrosis in children with chronic hepatitis. Materials and methods: Sixty-three consecutive children (40 boys, 23 girls, median age 9.3 years), with chronic hepatitis and thirty age matched volunteers underwent diffusion weighted MR imaging of the liver using a single shot echoplanar imaging with b-value = 0, 250, and 500 s/mm{sup 2}. Liver biopsy was obtained with calculation of METAVIR score. The ADC value of the liver was correlated with METAVIR score. Receiver operating characteristic curve was done for diagnosis and grading of hepatic fibrosis. Results: There was statistical difference in the mean ADC value between volunteers and patients with hepatic fibrosis (P = 0.001) and in patients with different grades of METAVIR scores (P = 0.002). There was correlation between the mean ADC value and METAVIR score (r = 0.807, P = 0.001). The cut off point to predict fibrosis (1.7 x 10{sup -3} mm{sup 2}/s) revealed 83% accuracy, 85% sensitivity, 82% specificity, 83% PPV, and 85% NPV. The area under the curve was 0.91 for F1, 0.85 for F2, 0.86 for F3 and 0.90 for F4. Conclusion: The apparent diffusion coefficient value is a promising quantitative parameter used for diagnosis and quantification of hepatic fibrosis in children with chronic hepatitis.

Prediction of survival by texture-based automated quantitative assessment of regional disease patterns on CT in idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Lee, Sang Min; Seo, Joon Beom; Oh, Sang Young; Lee, Sang Min; Kim, Namkug; Kim, Tae Hoon; Song, Jin Woo

2018-01-01

To retrospectively investigate whether the baseline extent and 1-year change in regional disease patterns on CT can predict survival of patients with idiopathic pulmonary fibrosis (IPF). A total of 144 IPF patients with CT scans at the time of diagnosis and 1 year later were included. The extents of five regional disease patterns were quantified using an in-house texture-based automated system. The fibrosis score was defined as the sum of the extent of honeycombing and reticular opacity. The Cox proportional hazard model was used to determine the independent predictors of survival. A total of 106 patients (73.6%) died during the follow-up period. Univariate analysis revealed that age, baseline forced vital capacity, total lung capacity, diffusing capacity of the lung for carbon monoxide, six-minute walk distance, desaturation , honeycombing, reticular opacity, fibrosis score, and interval changes in honeycombing and fibrosis score were significantly associated with survival. Multivariate analysis revealed that age, desaturation, fibrosis score and interval change in fibrosis score were significant independent predictors of survival (p = 0.003, <0.001, 0.001 and <0.001). The C-index for the developed model was 0.768. Texture-based, automated CT quantification of fibrosis can be used as an independent predictor of survival in IPF patients. (orig.)

Prediction of survival by texture-based automated quantitative assessment of regional disease patterns on CT in idiopathic pulmonary fibrosis

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Min; Seo, Joon Beom; Oh, Sang Young; Lee, Sang Min; Kim, Namkug [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Kim, Tae Hoon; Song, Jin Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Pulmonary and Critical Care Medicine, Seoul (Korea, Republic of)

2018-03-15

To retrospectively investigate whether the baseline extent and 1-year change in regional disease patterns on CT can predict survival of patients with idiopathic pulmonary fibrosis (IPF). A total of 144 IPF patients with CT scans at the time of diagnosis and 1 year later were included. The extents of five regional disease patterns were quantified using an in-house texture-based automated system. The fibrosis score was defined as the sum of the extent of honeycombing and reticular opacity. The Cox proportional hazard model was used to determine the independent predictors of survival. A total of 106 patients (73.6%) died during the follow-up period. Univariate analysis revealed that age, baseline forced vital capacity, total lung capacity, diffusing capacity of the lung for carbon monoxide, six-minute walk distance, desaturation{sub ,} honeycombing, reticular opacity, fibrosis score, and interval changes in honeycombing and fibrosis score were significantly associated with survival. Multivariate analysis revealed that age, desaturation, fibrosis score and interval change in fibrosis score were significant independent predictors of survival (p = 0.003, <0.001, 0.001 and <0.001). The C-index for the developed model was 0.768. Texture-based, automated CT quantification of fibrosis can be used as an independent predictor of survival in IPF patients. (orig.)

Grade IV fibrosis interferes in biliary drainage after Kasai procedure.

Science.gov (United States)

Salzedas-Netto, A A; Chinen, E; de Oliveira, D F; Pasquetti, A F; Azevedo, R A; da Silva Patricio, F F; Cury, E K; Gonzalez, A M; Vicentine, F P P; Martins, J L

2014-01-01

Biliary atresia (BA) is the most common cause of liver transplantation in children. The earlier the treatment is done, the better the prognosis. The aim is to evaluate the impact of late diagnosis in children with BA, including the histopathological findings and success rate of biliary drainage in patients submitted to hepatic portoenterostomy (HPE). A retrospective study of cases of BA in the Department of Pediatric Surgery, Federal University of São Paulo (UNIFESP) between 1998-2011. We found 63 cases of BA; of these, 42 underwent HPE and 21 were referred for liver transplantation. Clinic and pathologic data were evaluated. The HPE was performed with a mean age of 86.5 days, with 16.6% having the operation at 60 days or earlier; 59.2% between 61 and 90 days; and 23.8% after 90 days. Successful biliary drainage occurred in 31% of surgeries, Mean days when HPE drained was 69.1 days, and 94.3 days when the surgery did not drain (P = .05). All patients who were successfully drained, did not have grade IV fibrosis on histology. In cases in which surgery was performed after 60 days that had not drained, 25% had grade IV fibrosis on biopsy (P = .0469). The age of HPE relates to better prognosis of the disease. It was found that the rate of grade IV fibrosis is higher in no drainage patients. All patients with grade IV fibrosis had no biliary drainage. Copyright © 2014 Elsevier Inc. All rights reserved.

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)

Impact of liver fibrosis and fatty liver on T1rho measurements: A prospective study

International Nuclear Information System (INIS)

Xie, Shuang Shuang; Li, Qing; Cheng, Yue; Shen, Wen; Zhang, Yu; Zhuo, Zhi Zheng; Zhao, Guiming

2017-01-01

To investigate the liver T1rho values for detecting fibrosis, and the potential impact of fatty liver on T1rho measurements. This study included 18 healthy subjects, 18 patients with fatty liver, and 18 patients with liver fibrosis, who underwent T1rho MRI and mDIXON collections. Liver T1rho, proton density fat fraction (PDFF) and T2* values were measured and compared among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the T1rho values for detecting liver fibrosis. Liver T1rho values were correlated with PDFF, T2* values and clinical data. Liver T1rho and PDFF values were significantly different (p 0.05). T1rho MRI is useful for noninvasive detection of liver fibrosis, and may not be affected with the presence of fatty liver

Changes in soleus H-reflex during walking in middle-aged, healthy subjects

DEFF Research Database (Denmark)

Raffalt, Peter C; Alkjær, Tine; Simonsen, Erik B

2015-01-01

INTRODUCTION: To assess the effect of aging on stretch reflex modulation during walking, soleus H-reflexes obtained in 15 middle-aged (mean age 56.4±6.9 years) and 15 young (mean age 23.7±3.9 years) subjects were compared. METHODS: The H-reflex amplitude, muscle activity (EMG) of the soleus...... and tibialis anterior muscles, and EMG/H-reflex gain were measured during 4-km/h treadmill walking. RESULTS: The normalized H-reflex amplitude was lower in the swing phase for the middle-aged group, and there was no difference in muscle activity. EMG/H-reflex gain did not differ between groups. CONCLUSIONS: H......-reflex amplitude during walking was affected by aging, and changes during the swing phase could be seen in the middle-aged subjects. Subdividing the 2 age groups into groups of facilitated or suppressed swing-phase H-reflex revealed that the H-reflex amplitude modulation pattern in the group with facilitated swing...

Color change of composite resins subjected to accelerated artificial aging

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Denise Cremonezzi Tornavoi

2013-01-01

Conclusions: All composite resins presented unacceptable color changes after 382 h of aging and different composite resins with same hue, presented different colors before being subjected to the aging process (B2 and C2 and after (B2. It was also observed color difference within a group of the same composite resin and same hue.

Diagnosis of different liver fibrosis characteristics by blood tests in non-alcoholic fatty liver disease.

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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.

Active video games as an exercise tool for children with cystic fibrosis.

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O'Donovan, Cuisle; Greally, Peter; Canny, Gerard; McNally, Paul; Hussey, Juliette

2014-05-01

Active video games are used in many hospitals as exercise tools for children with cystic fibrosis. However, the exercise intensity associated with playing these games has not been examined in this population. Children with cystic fibrosis [n=30, aged 12.3 (2.6) years, 17 boys, BMI 17.7 (2.8) kg/m(2)] were recruited from outpatient clinics in Dublin hospitals. Age and gender matched control children were recruited from local schools. Oxygen consumption, metabolic equivalents (METs) calculated from resting V˙O2, and heart rate were measured while playing Nintendo Wii™ (Nintendo Co. Ltd., Tokyo, Japan) Sports Boxing and Nintendo Wii Fit Free Jogging using a portable indirect calorimeter (Oxycon Mobile). Playing Wii Boxing resulted in light intensity activity (2.46METs) while playing Wii Fit Free Jogging resulted in moderate intensity physical activity (4.44METs). No significant difference was seen between groups in the energy cost of playing active video games. Active video games are a useful source of light to moderate intensity physical activity in children with cystic fibrosis. © 2013.

IL-10 is significantly involved in HSP70-regulation of experimental subretinal fibrosis.

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Yang Yang

Full Text Available Subretinal fibrosis is directly related to severe visual loss, especially if occurs in the macula, and is frequently observed in advanced age-related macular degeneration and other refractory eye disorders such as diabetic retinopathy and uveitis. In this study, we analyzed the immunosuppressive mechanism of subretinal fibrosis using the novel animal model recently demonstrated. Both TLR2 and TLR4 deficient mice showed significant enlargement of subretinal fibrotic area as compared with wild-type mice. A single intraocular administration of heat shock protein 70 (HSP70, which is an endogenous ligand for TLR2 and TLR4, inhibited subretinal fibrosis in wild-type mice but not in TLR2 and TLR4-deficient mice. Additionally, HSP70 induced IL-10 production in eyes from wild-type mice but was impaired in both TLR2- and TLR4-deficient mice, indicating that HSP70-TLR2/TLR4 axis plays an immunomodulatory role in subretinal fibrosis. Thus, these results suggest that HSP70-TLR2/TLR4 axis is a new therapeutic target for subretinal fibrosis due to prognostic CNV.

The evaluation of selected insomnia predictors in adolescents and young adults with cystic fibrosis.

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Tomaszek, Lucyna; Cepuch, Grazyna; Pawlik, Lidia

2018-03-21

The purpose of the study was to assess the incidence of insomnia in adolescents and young adults with cystic fibrosis and its impact on the quality of life, and to examine whether demographic and clinical factors and negative emotional states are predictors of insomnia in these patients. The study was conducted among 95 cystic fibrosis patients aged 14-25 years. The study used a personal questionnaire survey, the Athens Insomnia Scale, the Cystic Fibrosis Quality of Life Questionnaire, the Hospital Anxiety and Depression Scale, and the Numeric Rating Scale. Insomnia was diagnosed in 38% of cystic fibrosis patients. In patients with insomnia, the level of anxiety (Me: 10 vs. 4; P=0.000) and depression (Me: 6.5 vs. 2; P=0.000) was significantly higher than in the good sleep quality group. The risk of insomnia increases as anxiety (OR: 4.31; 95% CI: 2.20 to 8.41) and depressive symptoms exacerbate (OR: 4.98; 95% CI: 1.84 to 13.43). Insomnia significantly worsens the quality of life in cystic fibrosis patients (ß =-0.5, P=0.000). Insomnia affects a large percentage of cystic fibrosis patients, and anxiety and depression are factors that increase the risk of insomnia. Insomnia decreases the quality of life in cystic fibrosis patients.

[Italian Cystic Fibrosis Register - Report 2010].

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Amato, Annalisa; Ferrigno, Luigina; Salvatore, Marco; Toccaceli, Virgilia

2016-01-01

The Italian National CF Registry (INCFR) is based on the official agreement between the clinicians of the Italian National Referral Centers for Cystic Fibrosis and the researchers of the Istituto Superiore di Sanità (National Center for Rare Diseases; National Center for Epidemiology, Surveillance and Health Care Promotion). OBJECTIVES The main aim of INCFR is to contribute to the improvement in CF patients health care and clinical management through: i. the estimates of CF prevalence and incidence in Italy; ii. the analyses of medium and long term clinical and epidemiological trends of the disesase; iii. the identification of the main health care needs at regional and national level to contribute to the Health Care programmes and to the distribution of resources. MATERIALS AND METHODS Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral Centers for Cystic Fibrosis in 2010. Data were sent by Centers by means of a specific software (Camilla, Ibis Informatica). The Italian National Referral Centers for Cystic Fibrosis sent a total of 5,271 individual records; 1,112 records were excluded from the analyses due to restricted inclusion criteria. The total number of patients included in INCFR for analyses is 4,159. RESULTS INCFR database includes all prevalent cases at 1th January 2010 as well as all new diagnoses done in 2010. The present Report has been organized into 9 sections. 1. Demography: estimated 2010 CF prevalence was 7/100,000 residents in Italy; 52% of the patients were male, CF distribution showed higher frequency in patients aged 7 to 35 years. In 2010, 48.9% of the patients were more than 18 years old. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (66.7%); a significant percentage of patients (11.4%) was diagnosed in adult-age. 3. New diagnoses (2010): new diagnoses were 168. Sixty-five percent of them was diagnosed before the second year of age and 17%in

Hepatosplenic volumetric assessment at MDCT for staging liver fibrosis

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Pickhardt, Perry J.; Malecki, Kyle; Hunt, Oliver F.; Beaumont, Claire; Kloke, John; Ziemlewicz, Timothy J.; Lubner, Meghan G. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

2017-07-15

To investigate hepatosplenic volumetry at MDCT for non-invasive prediction of hepatic fibrosis. Hepatosplenic volume analysis in 624 patients (mean age, 48.8 years; 311 M/313 F) at MDCT was performed using dedicated software and compared against pathological fibrosis stage (F0 = 374; F1 = 48; F2 = 40; F3 = 65; F4 = 97). The liver segmental volume ratio (LSVR) was defined by Couinaud segments I-III over segments IV-VIII. All pre-cirrhotic fibrosis stages (METAVIR F1-F3) were based on liver biopsy within 1 year of MDCT. LSVR and total splenic volumes increased with stage of fibrosis, with mean(±SD) values of: F0: 0.26 ± 0.06 and 215.1 ± 88.5 mm{sup 3}; F1: 0.25 ± 0.08 and 294.8 ± 153.4 mm{sup 3}; F2: 0.331 ± 0.12 and 291.6 ± 197.1 mm{sup 3}; F3: 0.39 ± 0.15 and 509.6 ± 402.6 mm{sup 3}; F4: 0.56 ± 0.30 and 790.7 ± 450.3 mm{sup 3}, respectively. Total hepatic volumes showed poor discrimination (F0: 1674 ± 320 mm{sup 3}; F4: 1631 ± 691 mm{sup 3}). For discriminating advanced fibrosis (≥F3), the ROC AUC values for LSVR, total liver volume, splenic volume and LSVR/spleen combined were 0.863, 0.506, 0.890 and 0.947, respectively. Relative changes in segmental liver volumes and total splenic volume allow for non-invasive staging of hepatic fibrosis, whereas total liver volume is a poor predictor. Unlike liver biopsy or elastography, these CT volumetric biomarkers can be obtained retrospectively on routine scans obtained for other indications. (orig.)

Psychological interventions for individuals with cystic fibrosis and their families.

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Goldbeck, Lutz; Fidika, Astrid; Herle, Marion; Quittner, Alexandra L

2014-06-18

With increasing survival estimates for individuals with cystic fibrosis, long-term management has become an important focus. Psychological interventions are largely concerned with adherence to treatment, emotional and social adaptation and health-related quality of life. We are unaware of any relevant systematic reviews. To determine whether psychological interventions for people with cystic fibrosis provide significant psychosocial and physical benefits in addition to standard medical care. Studies were identified from two Cochrane trials registers (Cystic Fibrosis and Genetic Disorders Group; Depression, Anxiety and Neurosis Group), Ovid MEDLINE and PsychINFO; unpublished trials were located through professional networks and Listserves. Most recent search of the Cystic Fibrosis and Genetic Disorders Group's register: 19 December 2013.Most recent search of the Depression, Anxiety and Neurosis Group's register: 12 November 2013. Randomised controlled studies of a broad range of psychological interventions evaluating subjective and objective health outcomes, such as quality of life or pulmonary function, in individuals of all ages with cystic fibrosis and their immediate family. We were interested in psychological interventions, including psychological methods within the scope of psychotherapeutic or psychosomatic mechanism of action (e.g. cognitive behavioural, cognitive, family systems or systemic, psycho-dynamic, or other, e.g. supportive, relaxation, or biofeedback), which were aimed at improving psychological and psychosocial outcomes (e.g. quality of life, levels of stress or distress, psychopathology, etc.), adaptation to disease management and physiological outcomes. Three authors were involved in selecting the eligible studies and two of these authors assessed their risk of bias. The review includes 16 studies (eight new studies included in this update) representing data from 556 participants. Studies are diverse in their design and their methods. They

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

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

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

2016-01-01

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

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

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

2016-11-18

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

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....

Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy

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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

CXC-type chemokines promote myofibroblast phenoconversion and prostatic fibrosis.

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Mehrnaz Gharaee-Kermani

Full Text Available Recent studies from our group suggest that extracellular matrix (ECM deposition and fibrosis characterize the peri-urethral prostate tissues of some men suffering from Lower Urinary Tract Symptoms (LUTS and that fibrosis may be a contributing factor to the etiology of LUTS. Fibrosis can generally be regarded as an errant wound-healing process in response to chronic inflammation, and several studies have shown that the aging prostate tissue microenvironment is rich with inflammatory cells and proteins. However, it is unclear whether these same inflammatory proteins, particularly CXC-type chemokines, can mediate myofibroblast phenoconversion and the ECM deposition necessary for the development of prostatic tissue fibrosis. To examine this, immortalized and primary prostate stromal fibroblasts treated with TGF-β1, CXCL5, CXCL8, or CXCL12 were evaluated morphologically by microscopy, by immunofluorescence and qRT-PCR for αSMA, collagen 1, vimentin, calponin, and tenascin protein and transcript expression, and by gel contraction assays for functional myofibroblast phenoconversion. The results of these studies showed that that immortalized and primary prostate stromal fibroblasts are induced to express collagen 1 and 3 and αSMA gene transcripts and proteins and to undergo complete and functional myofibroblast phenoconversion in response to CXC-type chemokines, even in the absence of exogenous TGF-β1. Moreover, CXCL12-mediated myofibroblast phenoconversion can be completely abrogated by inhibition of the CXCL12 receptor, CXCR4. These findings suggest that CXC-type chemokines, which comprise inflammatory proteins known to be highly expressed in the aging prostate, can efficiently and completely mediate myofibroblast phenoconversion and may thereby promote fibrotic changes in prostate tissue architecture associated with the development and progression of male lower urinary tract dysfunction.

[Diastolic dysfunction in the elderly subjects. Disease or a physiological manifestation of ageing?].

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Meluzín, J; Podroužková, H; Gregorová, Z; Panovský, R

2013-05-01

The purpose of this summary paper is to discuss the current knowledge of the impact of age on diastolic function of the left ventricle. Data from the literature: Reports published till this time have convincingly demonstrated a significant relationship of age to diastolic function of the left ventricle. Ageing is a physiological process accompanied by structural changes in both myocardium and arterial bed resulting in worsening of parameters characterizing the left ventricular diastolic function. This "physiological" diastolic dysfunction in the elderly subjects can be explained by the deterioration of passive left ventricular filling properties and by worsening of left ventricular relaxation. The detailed analysis of published reports shows problems in distiguishing this "physiological" diastolic dysfunction resulting from physiological tissue ageing from "pathological" diastolic dysfunction reflecting a disease of cardiovascular system. To interprete correctly values of parameters quantifying diastolic function of the left ventricle, one should take into account the age of subjects under the examination. Further studies are necessary to distinguish exactly "physiological" deterioration of diastolic function associated with ageing from really "pathological" diastolic dysfunction in the elderly subjects.

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

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E. B. Pavlinova

2016-01-01

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

Zinc supplementation suppresses the progression of bile duct ligation-induced liver fibrosis in mice.

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Shi, Fang; Sheng, Qin; Xu, Xinhua; Huang, Wenli; Kang, Y James

2015-09-01

Metallothionein (MT) gene therapy leads to resolution of liver fibrosis in mouse model, in which the activation of collagenases is involved in the regression of liver fibrosis. MT plays a critical role in zinc sequestration in the liver suggesting its therapeutic effect would be mediated by zinc. The present study was undertaken to test the hypothesis that zinc supplementation suppresses liver fibrosis. Male Kunming mice subjected to bile duct ligation (BDL) resulted in liver fibrosis as assessed by increased α-smooth muscle actin (α-SMA) and collagen I production/deposition in the liver. Zinc supplementation was introduced 4 weeks after BDL surgery via intragastric administration once daily for 2 weeks resulting in a significant reduction in the collagen deposition in the liver and an increase in the survival rate. Furthermore, zinc suppressed gene expression of α-SMA and collagen I and enhanced the capacity of collagen degradation, as determined by the increased activity of total collagenases and elevated mRNA and protein levels of MMP13. Therefore, the results demonstrate that zinc supplementation suppresses BDL-induced liver fibrosis through both inhibiting collagen production and enhancing collagen degradation. © 2014 by the Society for Experimental Biology and Medicine.

Lung-specific loss of α3 laminin worsens bleomycin-induced pulmonary fibrosis.

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Morales-Nebreda, Luisa I; Rogel, Micah R; Eisenberg, Jessica L; Hamill, Kevin J; Soberanes, Saul; Nigdelioglu, Recep; Chi, Monica; Cho, Takugo; Radigan, Kathryn A; Ridge, Karen M; Misharin, Alexander V; Woychek, Alex; Hopkinson, Susan; Perlman, Harris; Mutlu, Gokhan M; Pardo, Annie; Selman, Moises; Jones, Jonathan C R; Budinger, G R Scott

2015-04-01

Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the α3 laminin subunit was lost in fibrotic regions of the lung. To determine if these changes play a causal role in the development of fibrosis, we generated mice lacking the α3 laminin subunit specifically in the lung epithelium by crossing mice expressing Cre recombinase driven by the surfactant protein C promoter (SPC-Cre) with mice expressing floxed alleles encoding the α3 laminin gene (Lama3(fl/fl)). These mice exhibited no developmental abnormalities in the lungs up to 6 months of age, but, compared with control mice, had worsened mortality, increased inflammation, and increased fibrosis after the intratracheal administration of bleomycin. Similarly, the severity of fibrosis induced by an adenovirus encoding an active form of transforming growth factor-β was worse in mice deficient in α3 laminin in the lung. Taken together, our results suggest that the loss of α3 laminin in the lung epithelium does not affect lung development, but plays a causal role in the development of fibrosis in response to bleomycin or adenovirally delivered transforming growth factor-β. Thus, we speculate that the loss of the normal basement membrane organization of α3 laminin that we observe in fibrotic regions from the lungs of patients with pulmonary fibrosis contributes to their disease progression.

Iodine deficiency and subclinical hypothyroidism are common in cystic fibrosis patients.

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Naehrlich, Lutz; Dörr, Helmuth-Günther; Bagheri-Behrouzi, Azadeh; Rauh, Manfred

2013-04-01

Disorders of thyroid function have been inconsistently described in cystic fibrosis (CF) patients and in CF transmembrane regulator protein knockout animals. The literature lacks reports on iodine status of CF individuals. We hypothesize, that iodine deficiency is common in CF and account for abnormal thyroid function in CF patients. We investigated 129 children, adolescents, and adults with CF, who were living in the northern part of Bavaria/Germany. Malnutrition and lung function were analyzed. Urinary iodine excretion, TSH (thyroid-stimulating hormone), and ft4 (free thyroxine) were measured and set in relation to population-based, age-adjusted reference ranges. Subclinical hypothyroidism (normal fT4, elevated TSH) was found in 11.6% of subjects, and iodine deficiency in 83.7%. No correlations were found with age, BMI, status of malnutrition, or lung function. Dramatic iodine deficiency was found in our cohort of CF patients. This condition can cause subclinical hypothyroidism; therefore, an individual iodine supplementation program is necessary and should be started immediately. Crown Copyright © 2012. Published by Elsevier GmbH. All rights reserved.

Body composition and pulmonary function in Cystic Fibrosis

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Saba eSheikh

2014-04-01

Full Text Available Background: Lower body mass index (BMI is associated with worse pulmonary function in cystic fibrosis (CF. Hypothesis: Lean body mass (LBM is more strongly associated with pulmonary function than BMI is.Methods: Anthropometrics, body composition by dual x-ray absorptiometry, and pulmonary function were determined in pancreatic insufficient CF (PI-CF youth. Sex and age-adjusted Z-scores (BMI-Z, LBMI-Z, FMI-Z were generated for CF and controls. 1 Associations of BMI-Z with LBMI-Z and FMI-Z and 2 age-adjusted associations of BMI-Z, LBMI-Z, and FMI-Z with FEV1%-predicted were tested. Results: 208 PI-CF subjects had lower BMI-Z, LBMI-Z, FMI-Z compared to 390 controls. BMI-Z was associated with lower LBMI-Z (pConclusions: In PI-CF youth, deficits in LBM were apparent. At lower BMI percentiles, BMI may not accurately depict LBM in PI-CF. In under-nourished PI-CF youth this preservation of FM in preference to LBM is relevant since LBMI-Z, but not FMI-Z, is positively associated with FEV1%-predicted. LBMI is more strongly associated with lung function compared to BMI, especially in the undernourished child and adolescent with PI-CF.

Intensity of ADHD Symptoms and Subjective Feelings of Competence in School Age Children

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Hanc, Tomasz; Brzezinska, Anna Izabela

2009-01-01

The aim of this investigation was to assess how different levels of intensity of ADHD symptoms influence the development of the subjective feeling of competence in school age children. The sample was comprised of 62 children age 11 to 13. For the purpose of estimation of the subjective feeling of competence, The Feeling of Competence Questionnaire…

Plasma clearance of noradrenaline does not change with age in normal subjects

DEFF Research Database (Denmark)

Hilsted, J; Christensen, N J; Larsen, S

1985-01-01

Noradrenaline kinetics (plasma concentrations, plasma clearance and appearance rates) were investigated in seven elderly healthy subjects and in six young healthy subjects. Forearm venous plasma noradrenaline concentrations were higher in the elderly subjects compared with the young subjects. Pla....... Plasma clearance of noradrenaline was identical in the two groups. The increase in plasma noradrenaline concentration, with age, probably reflects an increased sympathetic nervous activity.......Noradrenaline kinetics (plasma concentrations, plasma clearance and appearance rates) were investigated in seven elderly healthy subjects and in six young healthy subjects. Forearm venous plasma noradrenaline concentrations were higher in the elderly subjects compared with the young subjects...

Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study

DEFF Research Database (Denmark)

Pincikova, T; Nilsson, Kristine Kahr; Moen, I E

2011-01-01

Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis...

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Physical exercise training for cystic fibrosis.

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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

Eradication of early P. aeruginosa infection in children age with cystic fibrosis: The early study.

Science.gov (United States)

Ratjen, Felix; Moeller, Alexander; McKinney, Martha L; Asherova, Irina; Alon, Nipa; Maykut, Robert; Angyalosi, Gerhild

2018-04-20

Antibiotic eradication treatment is the standard-of-care for cystic fibrosis (CF) patients with early Pseudomonas aeruginosa (Pa)-infection; however, evidence from placebo-controlled trials is limited. This double-blind, placebo-controlled trial randomised CF patients early Pa-infection to tobramycin inhalation solution (TOBI 300 mg) or placebo (twice daily) for 28 days with an optional cross-over on Day 35. Primary endpoint was proportion of patients having throat swabs/sputum free of Pa on Day 29. On Day 29, 84.6% patients in the TOBI versus 24.0% in the placebo group were Pa-free (p early Pa-infection with a favourable safety profile in young CF patients. NCT01082367. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Proteome analysis of Radiation-induced pulmonary fibrosis

International Nuclear Information System (INIS)

Song, Jie Young; Lim, Hee Soon; Kim, Hyung Doo; Shim, Ji Young; Han, Young Soo; Son, Hyeog Jin Son; Yun, Yeon Sook

2005-01-01

Pulmonary fibrosis is perhaps the most universal late effect of organ damage after both chemical insult and irradiation in the treatment of lung cancer. The use chemotherapy and radiation therapy, alone or combined, can be associated with clinically significant pulmonary toxicity, which leads to pneumonia and pulmonary fibrosis. It is also reported that about 100,000 people in the United States are suffered from pulmonary fibrosis. Therefore, pulmonary fibrosis will be more focused by medicinal researchers. Because current therapies, aimed at inhibiting pulmonary inflammation that often precedes fibrosis, are effective only in a minority of suffered patients, novel therapeutic methods are highly needed. Some researchers have used bleomycininduced pulmonary fibrosis as a basis for looking at the molecular mechanisms of fibrosis, and total gene expression was monitored using genomics method. However, radiation-induced pulmonary fibrosis has not been fully focused and investigated. Here, we have analyzed changes in gene expression in response to γ- irradiation by using proteomic analysis

Metal toxicity- a possible cause of idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Javed, M.S.; Gilani, R.

2011-01-01

Idiopathic pulmonary fibrosis is a fatal disease of unknown etiology. Attempts are being made in the world to understand the disease mechanism by knowing its causes. Present research is a part to that contribution. Concentrations of some toxic metals were estimated in the blood and lung tissues of the persons diagnosed to be the subject of idiopathic pulmonary fibrosis. IPF subjects were selected for this purpose which was admitted in different hospitals in Lahore. Blood samples were taken directly from the patients whereas lung tissue samples were collected from the relevant biopsy labs. Three control blood samples were also collected from healthy persons. The samples were digested with Conc. HNO/sub 3/ to make their solutions for the estimation of metals. The metals selected were Cu, Pb, Cd, Cr, Be, Zn, Al, As and Co. Atomic Absorption Spectrophotometer (AAS) was used to estimate the metal concentrations in the sample solutions. The mean values of the concentrations (ppm) of these metals in the blood samples were Cu (0.65), Pb(0.69), Cd(1.17), Cr(0.21), Be(0.67), Zn(6.31), Al(1.33), As(0.46) and Co(0.46). The mean values of the concentrations (ppm) of these metals in the lung tissue samples were Cu (1.57), Pb(1.01), Cd(1.70), Cr(0.46), Be(2.02), Zn(10.20), Al(1.68), As(0.83) and Co(0.65). The concentrations of these metals were also estimated in the blood samples of control healthy persons and compared with the subjects. The difference of concentrations (ppm) in the blood samples of IPF subjects and Control Maximum (Mean Subjects - Control Max.) were Cu (0.50), Pb(0.62), Cd(1.17), Cr(0.21), Be(0.56), Zn(5.06), Al(1.31), As(0.46) and Co(0.46). Comparison of the mean values of concentrations of metals in blood samples of IPF subjects with the maximum concentration of metals in the blood samples of control healthy persons shows that metals levels are higher in the subjects than the control ones. i.e. Cu(76.92%), Pb(89.6%), Cd(100%), Cr(100%), Be(83.58%), Zn(80

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Macrophage recruitment by fibrocystin-defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis.

Science.gov (United States)

Locatelli, Luigi; Cadamuro, Massimiliano; Spirlì, Carlo; Fiorotto, Romina; Lecchi, Silvia; Morell, Carola Maria; Popov, Yury; Scirpo, Roberto; De Matteis, Maria; Amenduni, Mariangela; Pietrobattista, Andrea; Torre, Giuliano; Schuppan, Detlef; Fabris, Luca; Strazzabosco, Mario

2016-03-01

Congenital hepatic fibrosis (CHF) is a disease of the biliary epithelium characterized by bile duct changes resembling ductal plate malformations and by progressive peribiliary fibrosis, in the absence of overt necroinflammation. Progressive liver fibrosis leads to portal hypertension and liver failure; however, the mechanisms leading to fibrosis in CHF remain elusive. CHF is caused by mutations in PKHD1, a gene encoding for fibrocystin, a ciliary protein expressed in cholangiocytes. Using a fibrocystin-defective (Pkhd1(del4/del4)) mouse, which is orthologous of CHF, we show that Pkhd1(del4/del4) cholangiocytes are characterized by a β-catenin-dependent secretion of a range of chemokines, including chemokine (C-X-C motif) ligands 1, 10, and 12, which stimulate bone marrow-derived macrophage recruitment. We also show that Pkhd1(del4/del4) cholangiocytes, in turn, respond to proinflammatory cytokines released by macrophages by up-regulating αvβ6 integrin, an activator of latent local transforming growth factor-β1. While the macrophage infiltrate is initially dominated by the M1 phenotype, the profibrogenic M2 phenotype increases with disease progression, along with the number of portal myofibroblasts. Consistent with these findings, clodronate-induced macrophage depletion results in a significant reduction of portal fibrosis and portal hypertension as well as of liver cysts. Fibrosis can be initiated by an epithelial cell dysfunction, leading to low-grade inflammation, macrophage recruitment, and collagen deposition; these findings establish a new paradigm for biliary fibrosis and represent a model to understand the relationship between cell dysfunction, parainflammation, liver fibrosis, and macrophage polarization over time. © 2015 by the American Association for the Study of Liver Diseases.

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

Science.gov (United States)

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

2010-06-01

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

Age-related changes of diffusional anisotropy in the cerebral white matter in normal subjects

International Nuclear Information System (INIS)

Hanyu, Haruo; Asano, Tetsuichi; Ogawa, Kimikazu; Takasaki, Masaru; Shindo, Hiroaki; Kakizaki, Dai; Abe, Kimihiko

1997-01-01

To investigate age-related changes of diffusional anisotropy in the cerebral white matter, we performed diffusion-weighted MRI studies in 21 normal subjects aged 25 to 96 years. The anisotropic rations (ARs), defined as the apparent diffusion coefficients perpendicular to the nerve fibers to those parallel to the nerve fibers, were significantly higher in elderly than in young subjects in the anterior and posterior white matter surrounding the lateral ventricle. Moreover, significant correlation between age and AR was found in the anterior white matter. The ventricular index (VI) measured on MRI, as a quantitative indicator of brain atrophy, was significantly higher in elderly than younger subjects, and significantly correlated with AR in the anterior white matter. Multiple regression analysis demonstrated that the VI showed the highest correlation for AR. On the other hand, there was no significant correlations between ARs in the corpus callosum and age. These results suggest that morphological changes in the myelin and axon in the white matter occur in elderly normal subjects, probably due to neuronal loss with aging. (author)

Inhibition of muscle fibrosis results in increases in both utrophin levels and the number of revertant myofibers in Duchenne muscular dystrophy.

Science.gov (United States)

Levi, Oshrat; Genin, Olga; Angelini, Corrado; Halevy, Orna; Pines, Mark

2015-09-15

Duchenne Muscular Dystrophy is characterized by: near absence of dystrophin in skeletal muscles; low percentage of revertant myofibers; up-regulation of utrophin synthesis; and a high degree of muscle fibrosis. In patient quadriceps femoris biopsies (n = 6, ages between 3-9 years) an inverse correlation was observed between the levels of collagen type I - representing fibrosis - and the levels of utrophin. This correlation was independent of the patient's age and was observed in the entire muscle biopsy sections. In the mdx mice diaphragm (n = 6/group), inhibition of fibrosis by halofuginone resulted in increases in the levels of utrophin. The utrophin/fibrosis relationships were not limited to collagen type I, but also applied to other constituents of the fibrosis machinery. The inverse correlation was found also in old mdx mice with established fibrosis. In addition, inhibition of collagen type I levels was associated with increases in the numbers of revertant myofibers, both as single myofibers and in clusters in the diaphragm and the gastrocnemius. In summary, our results demonstrate an inverse correlation between the level of muscle fibrosis and the level of utrophin and that of the number of revertant myofibers. These findings may reveal common links between the fibrotic and utrophin-synthesis pathways and offer new insights into the regulation of utrophin synthesis.

Structural and perfusion magnetic resonance imaging of the lung in cystic fibrosis

International Nuclear Information System (INIS)

Amaxopoulou, Christina; Gnannt, Ralph; Kellenberger, Christian J.; Higashigaito, Kai; Jung, Andreas

2018-01-01

Because of its absence of ionising radiation and possibility for obtaining functional information, MRI is promising for assessing lung disease in children who require repetitive imaging for long-term follow-up. To describe MRI findings in children with cystic fibrosis and evaluate semi-quantitative dynamic contrast-enhanced lung perfusion. We retrospectively compared lung MRI in 25 children and young adults with cystic fibrosis (median age 3.7 years) to 12 children (median age 2 years) imaged for other pathologies. MRI at 1.5 T included respiratory-gated sequences and contrast-enhanced lung perfusion imaging. We described and graded any morphologic change. Signal enhancement and time to peak values of perfusion abnormalities were compared to those of normally enhancing lung parenchyma. Frequent findings in patients with cystic fibrosis were bronchial wall thickening (24/25, 96%), areas of consolidation (22/25, 88%), enlarged lymph nodes (20/25, 80%), bronchiectasis (5/25, 20%) and mucus plugging (3/25, 12%). Compared to normally enhancing lung, perfusion defects (21/25, 84%), characterised by decreased enhancement, showed prolonged time to peak. Areas of consolidation showed increased enhancement. While time to peak of procedure-related atelectasis was not significantly different from that of normal lung, disease-related consolidation showed prolonged time to peak (P=0.01). Lung MRI demonstrates structural and perfusion abnormalities in children and young people with cystic fibrosis. Semi-quantitative assessment of dynamic contrast-enhanced perfusion imaging might allow differentiation between procedure-related atelectasis and disease-related consolidation. (orig.)

Structural and perfusion magnetic resonance imaging of the lung in cystic fibrosis

Energy Technology Data Exchange (ETDEWEB)

Amaxopoulou, Christina; Gnannt, Ralph; Kellenberger, Christian J. [University Children' s Hospital Zuerich, Department of Diagnostic Imaging, Zuerich, CH (Switzerland); University Children' s Hospital Zuerich, Children' s Research Center, Zuerich (Switzerland); Higashigaito, Kai [University Hospital Zuerich, Institute of Diagnostic and Interventional Radiology, Zuerich (Switzerland); Jung, Andreas [University Children' s Hospital Zuerich, Children' s Research Center, Zuerich (Switzerland); University Children' s Hospital Zuerich, Division of Pneumology, Zuerich (Switzerland)

2018-02-15

Because of its absence of ionising radiation and possibility for obtaining functional information, MRI is promising for assessing lung disease in children who require repetitive imaging for long-term follow-up. To describe MRI findings in children with cystic fibrosis and evaluate semi-quantitative dynamic contrast-enhanced lung perfusion. We retrospectively compared lung MRI in 25 children and young adults with cystic fibrosis (median age 3.7 years) to 12 children (median age 2 years) imaged for other pathologies. MRI at 1.5 T included respiratory-gated sequences and contrast-enhanced lung perfusion imaging. We described and graded any morphologic change. Signal enhancement and time to peak values of perfusion abnormalities were compared to those of normally enhancing lung parenchyma. Frequent findings in patients with cystic fibrosis were bronchial wall thickening (24/25, 96%), areas of consolidation (22/25, 88%), enlarged lymph nodes (20/25, 80%), bronchiectasis (5/25, 20%) and mucus plugging (3/25, 12%). Compared to normally enhancing lung, perfusion defects (21/25, 84%), characterised by decreased enhancement, showed prolonged time to peak. Areas of consolidation showed increased enhancement. While time to peak of procedure-related atelectasis was not significantly different from that of normal lung, disease-related consolidation showed prolonged time to peak (P=0.01). Lung MRI demonstrates structural and perfusion abnormalities in children and young people with cystic fibrosis. Semi-quantitative assessment of dynamic contrast-enhanced perfusion imaging might allow differentiation between procedure-related atelectasis and disease-related consolidation. (orig.)

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

Science.gov (United States)

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

2017-02-01

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

Feasibility, tolerability and safety of pediatric hyperpolarized {sup 129}Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis

Energy Technology Data Exchange (ETDEWEB)

Walkup, Laura L.; Watters, Erin; Ruppert, Kai [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); Thomen, Robert P.; Woods, Jason C. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); Washington University in St. Louis, Department of Physics, St. Louis, MO (United States); Akinyi, Teckla G.; Cleveland, Zackary I. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Division of Pulmonary Medicine and Department of Radiology, Cincinnati, OH (United States); University of Cincinnati, Biomedical Engineering Program, Cincinnati, OH (United States); Clancy, John P. [Cincinnati Children' s Hospital Medical Center, Division of Pulmonary Medicine, Cincinnati, OH (United States)

2016-11-15

Hyperpolarized {sup 129}Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. To assess the feasibility, safety and tolerability of hyperpolarized {sup 129}Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. Seventeen healthy control subjects (ages 6-15 years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys) underwent {sup 129}Xe MRI, receiving up to three doses of {sup 129}Xe gas prepared by either a commercially available or a homebuilt {sup 129}Xe polarizer. Subject heart rate and SpO{sub 2} were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI. All children tolerated multiple doses of {sup 129}Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO{sub 2} (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO{sub 2} values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following {sup 129}Xe MRI, but all were deemed unrelated to the study. The feasibility, safety and tolerability of {sup 129}Xe MRI has been assessed in a small group of children as young as 6 years. SpO{sub 2} changes were consistent with the expected physiological effects of a short anoxic breath

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

Science.gov (United States)

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

2015-08-01

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

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1994-12-15

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

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

International Nuclear Information System (INIS)

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

1994-01-01

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

Liver manifestations of cystic fibrosis

International Nuclear Information System (INIS)

Akata, Deniz; Akhan, Okan

2007-01-01

Chronic liver disease is one of the major complications of cystic fibrosis (CF). Significant liver disease is seen in 13-25% of children with CF. Improved life expectancy and prolonged follow-up have favored better characterization of the hepatic manifestations of CF and allowed direct observation of an increasing number of liver-related events. Liver disease typically develops in the first decade of life, with the incidence dropping rapidly after the age of 10 years. The wide spectrum of liver disease ranging from asymptomatic gallbladder abnormalities to biliary cirrhosis will be reviewed in this article

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.

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

International Nuclear Information System (INIS)

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

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-05-15

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

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

International Nuclear Information System (INIS)

Tassi, Eduardo Marinho; Continentino, Marcelo Abramoff; Nascimento, Emília Matos do; Pereira, Basílio de Bragança; Pedrosa, Roberto Coury

2014-01-01

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

THE NATIONAL CONSENSUS PROJECT* «CYSTIC FIBROSIS: DEFINITION, DIAGNOSTIC CRITERIA, AND THERAPY». SECTION «INHALATION THERAPY» (ABRIDGED

Directory of Open Access Journals (Sweden)

Ye. L. Amelina

2014-01-01

Full Text Available The pulmonary drug administration for the treatment of a pulmonary affection in cystic fibrosis is highly effective. This consensus document summarizes data on inhalation intake of bronchodilators, mucolytics, anti-inflammatory drugs, including glucocorticoids, recommended for use in cystic fibrosis patients of all age groups in the territory of the Russian Federation

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

Individualized unsupervised exercise programs and chest physiotherapy in children with cystic fibrosis

Directory of Open Access Journals (Sweden)

Bogdan ALMĂJAN-GUȚĂ

2013-12-01

Full Text Available Traditionally, physiotherapy for cystic fibrosis focused mainly on airway clearance (clearing mucus from the lungs. This still makes up a large part of daily treatment, but the role of the physiotherapist in cystic fibrosis has expanded to include daily exercise, inhalation therapy, posture awareness and, for some, the management of urinary incontinence. The purpose of this study is to demonstrate the necessity and the efficiency of various methods of chest physiotherapy and individualized unsupervised exercise program, in the improvement of body composition and physical performance. This study included 12 children with cystic fibrosis, with ages between 8-13 years. Each subject was evaluated in terms of body composition, effort capacity and lower body muscular performance, at the beginning of the study and after 12 months.The intervention consisted in classic respiratory clearance and physiotherapy techniques (5 times a week and an individualized unsupervised exercise program (3 times a week. After 12 months we noticed a significant improvement of the measured parameters: body weight increased from 32.25±5.5 to 33.53±5.4 kg (p <0.001, skeletal muscle mass increased from a mean of 16.04±4.1 to 17.01±4.2 (p<0.001, the fitness score, increased from a mean of 71±3.8 points to73±3.8, (p<0.001 and power and force also registered positive evolutions (from 19.3±2.68 to 21.65±2.4 W/kg and respectively 19.68±2.689 to 20.81±2.98 N/kg.The association between physiotherapy procedures and an individualized (after a proper clinical assessment unsupervised exercise program, proved to be an effective, relatively simple and accessible (regardless of social class intervention.

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 ...

APRI: A simple bedside marker for advanced fibrosis that can avoid ...

African Journals Online (AJOL)

Aspartate aminotransferase-toplatelet ratio index (APRI) is a simpler calculation than NFS, but has never been studied in patients with non-alcoholic fatty liver disease (NAFLD). Aim. To validate APRI as a non-invasive marker of liver fibrosis in subjects with NAFLD to be used in clinical practice. Design/Methods. The cohort ...

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

Ultramicronized palmitoylethanolamide (PEA-um(®)) in the treatment of idiopathic pulmonary fibrosis.

Science.gov (United States)

Di Paola, Rosanna; Impellizzeri, Daniela; Fusco, Roberta; Cordaro, Marika; Siracusa, Rosalba; Crupi, Rosalia; Esposito, Emanuela; Cuzzocrea, Salvatore

2016-09-01

Pulmonary fibrosis is a chronic condition characterized by progressive scarring of lung parenchyma. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (PEA-um(®)), an endogenous fatty acid amide, in mice subjected to idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis was induced in male mice by a single intratracheal administration of saline with bleomycin sulphate (1mg/kg body weight) in a volume of 100μL. PEA-um(®) was injected intraperitoneally at 1, 3 or 10mg/kg 1h after bleomycin instillation and daily thereafter. Animals were sacrificed after 7 and 21days by pentobarbitone overdose. One cohort of mice was sacrificed after seven days of bleomycin administration, followed by bronchoalveloar lavage and determination of myeloperoxidase activity, lung edema and histopathology features. In the 21-day cohort, mortality was assessed daily, and surviving mice were sacrificed followed by the above analyses together with immunohistochemical localization of CD8, tumor necrosis factor-α, CD4, interleukin-1β, transforming growth factor-β, inducible nitric oxide synthase and basic fibroblast growth factor. Compared to bleomycin-treated mice, animals that received also PEA-um(®) (3 or 10mg/kg) had significantly decreased weight loss, mortality, inflammation, lung damage at the histological level, and lung fibrosis at 7 and 21days. PEA-um(®) (1mg/kg) did not significantly inhibit the inflammation response and lung fibrosis. This study demonstrates that PEA-um(®) (3 and 10mg/kg) reduces the extent of lung inflammation in a mouse model of idiopathic pulmonary fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fibrosis of Two: Epithelial Cell-Fibroblast Interactions in Pulmonary Fibrosis

Science.gov (United States)

Sakai, Norihiko; Tager, Andrew M.

2013-01-01

Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function. IPF is now thought to result from wound-healing processes that, although initiated to protect the host from injurious environmental stimuli, lead to pathological fibrosis due to these processes becoming aberrant or over-exuberant. Although the environmental stimuli that trigger IPF remain to be identified, recent evidence suggests that they initially injure the alveolar epithelium. Repetitive cycles of epithelial injury and resultant alveolar epithelial cell death provoke the migration, proliferation, activation and myofibroblast differentiation of fibroblasts, causing the accumulation of these cells and the extracellular matrix that they synthesize. In turn, these activated fibroblasts induce further alveolar epithelial cell injury and death, thereby creating a vicious cycle of pro-fibrotic epithelial cell-fibroblast interactions. Though other cell types certainly make important contributions, we focus here on the “pas de deux” (steps of two), or perhaps more appropriate to IPF pathogenesis, the “folie à deux” (madness of two) of epithelial cells and fibroblasts that drives the progression of pulmonary fibrosis. We describe the signaling molecules that mediate the interactions of these cell types in their “fibrosis of two”, including transforming growth factor-β, connective tissue growth factor, sonic hedgehog, prostaglandin E2, angiotensin II and reactive oxygen species. PMID:23499992

A comparison of MR elastography and {sup 31}P MR spectroscopy with histological staging of liver fibrosis

Energy Technology Data Exchange (ETDEWEB)

Godfrey, Edmund M. [St James' Hospital, Leeds (United Kingdom); St James' Hospital, Department of Radiology, Leeds (United Kingdom); Patterson, Andrew J.; Priest, Andrew N.; Davies, Susan E.; Joubert, Ilse; Krishnan, Anant S.; Shaw, Ashley S.; Alexander, Graeme J.; Allison, Michael E.; Griffiths, William J.H.; Gimson, Alexander E.S. [Addenbrooke' s Hospital, Cambridge (United Kingdom); Griffin, Nyree [St Thomas' s Hospital, London (United Kingdom); Lomas, David J. [University of Cambridge, Department of Radiology, Cambridge (United Kingdom)

2012-12-15

Conventional imaging techniques are insensitive to liver fibrosis. This study assesses the diagnostic accuracy of MR elastography (MRE) stiffness values and the ratio of phosphomonoesters (PME)/phosphodiesters (PDE) measured using {sup 31}P spectroscopy against histological fibrosis staging. The local research ethics committee approved this prospective, blinded study. A total of 77 consecutive patients (55 male, aged 49 {+-} 11.5 years) with a clinical suspicion of liver fibrosis underwent an MR examination with a liver biopsy later the same day. Patients underwent MRE and {sup 31}P spectroscopy on a 1.5 T whole body system. The liver biopsies were staged using an Ishak score for chronic hepatitis or a modified NAS fibrosis score for fatty liver disease. MRE increased with and was positively associated with fibrosis stage (Spearman's rank = 0.622, P < 0.001). PME/PDE was not associated with fibrosis stage (Spearman's rank = -0.041, p = 0.741). Area under receiver operating curves for MRE stiffness values were high (range 0.75-0.97). The diagnostic utility of PME/PDE was no better than chance (range 0.44-0.58). MRE-estimated liver stiffness increases with fibrosis stage and is able to dichotomise fibrosis stage groupings. We did not find a relationship between {sup 31}P MR spectroscopy and fibrosis stage. circle Magnetic resonance elastography (MRE) and MR spectroscopy can both assess the liver. (orig.)

Breakdown in Breathing: The Complexities of Cystic Fibrosis

Science.gov (United States)

... Healthier Lungs in Kids Wise Choices Living with Cystic Fibrosis In between checkups, practice good self-care and ... Links What Is Cystic Fibrosis? Learning About Cystic Fibrosis NIH Cystic Fibrosis Fact Sheet Genetic and Rare Diseases Information ...

Value of 3 Tesla diffusion-weighted magnetic resonance imaging for assessing liver fibrosis.

Science.gov (United States)

Papalavrentios, Lavrentios; Sinakos, Emmanouil; Chourmouzi, Danai; Hytiroglou, Prodromos; Drevelegas, Konstantinos; Constantinides, Manos; Drevelegas, Antonios; Talwalkar, Jayant; Akriviadis, Evangelos

2015-01-01

Limited data are available regarding the role of magnetic resonance imaging (MRI), particularly the new generation 3 Tesla technology, and especially diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our pilot study was to assess the clinical performance of the apparent diffusion coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). 18 patients with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm 2 . ADC was measured in four locations in the liver and the mean ADC value was used for analysis. Staging of fibrosis was performed according to the METAVIR system. The median age of patients was 52 years (range 23-73). The distribution of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5), 4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm 2 (r= -0.30, P=0.27). However it was significantly associated with ADC at b value of 0-1000 s/mm 2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm 2 ) the area under receiver-operating characteristic curve was 0.93 for fibrosis stage ≥3 and the optimal ADC cut-off value was 1.16 ×10 -3 mm 2 /s. 3 Tesla DWI can possibly predict the presence of advanced fibrosis in patients with NAFLD.

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....

Urinary incontinence in patients with cystic fibrosis.

Science.gov (United States)

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

2016-01-01

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

Feeling old today? Daily health, stressors, and affect explain day-to-day variability in subjective age.

Science.gov (United States)

Kotter-Grühn, Dana; Neupert, Shevaun D; Stephan, Yannick

2015-01-01

Subjective age is an important correlate of health, well-being, and longevity. So far, little is known about short-term variability in subjective age and the circumstances under which individuals feel younger/older in daily life. This study examined whether (a) older adults' felt age fluctuates on a day-to-day basis, (b) daily changes in health, stressors, and affect explain fluctuations in felt age, and (c) the daily associations between felt age and health, stressors, or affect are time-ordered. Using an eight-day daily diary approach, N = 43 adults (60-96 years, M = 74.65, SD = 8.19) filled out daily questionnaires assessing subjective age, health, daily stressors, and affect. Data were analysed using multilevel modelling. Subjective age, health, daily stressors, affect. Intra-individual variability in felt age was not explained by time but by short-term variability in other variables. Specifically, on days when participants experienced more than average health problems, stress, or negative affect they felt older than on days with average health, stress, or negative affect. No time-ordered effects were found. Bad health, many stressors, and negative affective experiences constitute circumstances under which older adults feel older than they typically do. Thus, daily measures of subjective age could be markers of health and well-being.

IL-4 polymorphisms, HRCT score and lung tissue markers in idiopathic pulmonary fibrosis

Czech Academy of Sciences Publication Activity Database

Vašáková, M.; Šterclová, M.; Matěj, R.; Olejár, Tomáš; Kolesár, L.; Skibová, J.; Stříž, I.

2013-01-01

Roč. 74, č. 10 (2013), s. 1346-1351 ISSN 0198-8859 Institutional support: RVO:67985823 Keywords : IL-4 * gene polymorphism * idiopathic pulmonary fibrosis * PAR-2 * CD124 * TGF beta * YY-1 * TSLP Subject RIV: FC - Pulmology Impact factor: 2.282, year: 2013

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

Vitamin A supplementation for cystic fibrosis.

Science.gov (United States)

Bonifant, Catherine M; Shevill, Elizabeth; Chang, Anne B

2014-05-14

People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice. To determine if vitamin A supplementation in children and adults with cystic fibrosis:1. reduces the frequency of vitamin A deficiency disorders;2. improves general and respiratory health;3. increases the frequency of vitamin A toxicity. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 07 April 2014. All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency. No relevant studies for inclusion were identified in the search. No studies were included in this review. As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of

Feasibility, tolerability and safety of pediatric hyperpolarized "1"2"9Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis

International Nuclear Information System (INIS)

Walkup, Laura L.; Watters, Erin; Ruppert, Kai; Thomen, Robert P.; Woods, Jason C.; Akinyi, Teckla G.; Cleveland, Zackary I.; Clancy, John P.

2016-01-01

Hyperpolarized "1"2"9Xe is a promising contrast agent for MRI of pediatric lung function, but its safety and tolerability in children have not been rigorously assessed. To assess the feasibility, safety and tolerability of hyperpolarized "1"2"9Xe gas as an inhaled contrast agent for pediatric pulmonary MRI in healthy control subjects and in children with cystic fibrosis. Seventeen healthy control subjects (ages 6-15 years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys) underwent "1"2"9Xe MRI, receiving up to three doses of "1"2"9Xe gas prepared by either a commercially available or a homebuilt "1"2"9Xe polarizer. Subject heart rate and SpO_2 were monitored for 2 min post inhalation and compared to resting baseline values. Adverse events were reported via follow-up phone call at days 1 and 30 (range ±7 days) post-MRI. All children tolerated multiple doses of "1"2"9Xe, and no children withdrew from the study. Relative to baseline, most children who received a full dose of gas for imaging (10 of 12 controls and 8 of 11 children with cystic fibrosis) experienced a nadir in SpO_2 (mean -6.0 ± standard deviation 7.2%, P≤0.001); however within 2 min post inhalation SpO_2 values showed no significant difference from baseline (P=0.11). There was a slight elevation in heart rate (mean +6.6 ± 13.9 beats per minute [bpm], P=0.021), which returned from baseline within 2 min post inhalation (P=0.35). Brief side effects related to the anesthetic properties of xenon were mild and quickly resolved without intervention. No serious or severe adverse events were observed; in total, four minor adverse events (14.3%) were reported following "1"2"9Xe MRI, but all were deemed unrelated to the study. The feasibility, safety and tolerability of "1"2"9Xe MRI has been assessed in a small group of children as young as 6 years. SpO_2 changes were consistent with the expected physiological effects of a short anoxic breath-hold, and other mild side effects were

Serum YKL-40 is increased in patients with hepatic fibrosis

DEFF Research Database (Denmark)

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

2000-01-01

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

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.

Taurine attenuates radiation-induced lung fibrosis in C57/Bl6 fibrosis prone mice.

LENUS (Irish Health Repository)

Robb, W B

2010-03-01

The amino acid taurine has an established role in attenuating lung fibrosis secondary to bleomycin-induced injury. This study evaluates taurine\\'s effect on TGF-beta1 expression and the development of lung fibrosis after single-dose thoracic radiotherapy.

Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer

Czech Academy of Sciences Publication Activity Database

Polášek, Miloslav; Yang, Y.; Schühle, D. T.; Yaseen, M. A.; Kim, Y. R.; Sung, Y. S.; Guimaraes, A. R.; Caravan, P.

2017-01-01

Roč. 7, Aug 14 (2017), č. článku 8114. ISSN 2045-2322 Institutional support: RVO:61388963 Keywords : fibrosis * molecular imaging * pancreatic cancer Subject RIV: FD - Oncology ; Hematology OBOR OECD: Oncology Impact factor: 4.259, year: 2016 https://www.nature.com/ articles /s41598-017-08838-6

Vitamin A intake and serum retinol levels in children and adolescents with cystic fibrosis

NARCIS (Netherlands)

Woestenenk, JW; Broos, Nancy; Stellato, Rebecca K; Arets, Hubertus G M; van der Ent, Cornelis K.; Houwen, RHJ

2016-01-01

BACKGROUND: Pancreatic insufficient cystic fibrosis (CF) patients receive vitamin A supplementation according to CF-specific recommendations to prevent deficiencies. Whether current recommendations are optimal for preventing both deficiency and toxicity is a subject of debate. We assessed the

Salivary alpha amylase activity in human beings of different age groups subjected to psychological stress.

Science.gov (United States)

Sahu, Gopal K; Upadhyay, Seema; Panna, Shradha M

2014-10-01

Salivary alpha-amylase (sAA) has been proposed as a sensitive non-invasive biomarker for stress-induced changes in the body that reflect the activity of the sympathetic nervous system. Though several experiments have been conducted to determine the validity of this salivary component as a reliable stress marker in human subjects, the effect of stress induced changes on sAA level in different age groups is least studied. This article reports the activity of sAA in human subjects of different age groups subjected to psychological stress induced through stressful video clip. Differences in sAA level based on sex of different age groups under stress have also been studied. A total of 112 subjects consisting of both the male and female subjects, divided into two groups on basis of age were viewed a video clip of corneal transplant surgery as stressor. Activity of sAA from saliva samples of the stressed subjects were measured and compared with the activity of the samples collected from the subjects before viewing the clip. The age ranges of subjects were 18-25 and 40-60 years. The sAA level increased significantly in both the groups after viewing the stressful video. The increase was more pronounced in the younger subjects. The level of sAA was comparatively more in males than females in the respective groups. No significant change in sAA activity was observed after viewing the soothed video clip. Significant increase of sAA level in response to psychological stress suggests that it might act as a reliable sympathetic activity biochemical marker in different stages of human beings.

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-12-15

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

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

Directory of Open Access Journals (Sweden)

Farinet Catherine L

2006-05-01

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

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

Science.gov (United States)

Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan

2017-07-01

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

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

Directory of Open Access Journals (Sweden)

Cuiyuan Huang

2017-07-01

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

Small cardiac lesions: fibrosis of papillary muscles and focal cardiac myocytolysis

Energy Technology Data Exchange (ETDEWEB)

Steer, A [Hijiyanna Park, Hiroshima JP; Nakashima, N; Kawashima, T; Lee, K K; Danzig, M D; Robertson, T L; Dock, D S

1977-11-01

Three types of small cardiac lesions were described and illustrated: (1) focal type of papillary muscle fibrosis, evidently a healed infarct of the papillary muscle present in 13% of the autopsies, is a histologically characteristic lesion associated with coronary artery disease and healed myocardial infarction; (2) diffuse type of papillary muscle fibrosis, probably an aging change present in almost half of the autopsies, is associated with sclerosis of the arteries in the papillary muscle, is identifiable histologically; and apparently is not associated with any cardiac abnormality; and (3) focal cardiac myocytolysis, a unique histologic lesion, usually multifocal without predilection for any area of the heart, is associated with ischemic heart disease, death due to cancer complicated by non-bacterial thrombotic endocarditis and microthrombi in small cardiac arteries as well as with other diseases. Differentiation of the 2 types of papillary muscle fibrosis is important in the study of papillary muscle and mitral valve dysfunction. Focal cardiac myocytolysis may contribute to the fatal extension of myocardial infarcts.

Small cardiac lesions: fibrosis of papillary muscles and focal cardiac myocytolysis

Energy Technology Data Exchange (ETDEWEB)

Steer, A; Nakashima, T; Kawashima, T; Lee, K K; Danzig, M D; Robertson, T L; Dock, D S

1977-11-01

Three types of small cardiac lesions were described and illustrated: (1) focal type of papillary muscle fibrosis, evidently a healed infarct of the papillary muscle present in 13% of the autopsies, is a histologically characteristic lesion associated with coronary artery disease and healed myocardial infarction, (2) diffuse type of papillary muscle fibrosis, probably an aging change present in almost half of the autopsies, is associated with sclerosis of the arteries in the papillary muscle, is identifiable histologically, and apparently is not associated with any cardiac abnormality, and (3) focal cardiac myochtolysis, a unique histologic lesion, usually multifocal without predilection for any area of the heart, is associated with ischemic heart disease, death due to cancer complicated by nonbacterial thrombotic endocarditis and microthrombi in small cardiac arteries as well as with other diseases. Differentiation of the 2 types of papillary muscle fibrosis is important in the study of papillary muscle and mitral valve dysfunction. Focal cardiac myocytolysis may contribute to the fatal extension of myocardial infarcts.

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

Science.gov (United States)

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

2003-09-01

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

Serum adiponectin is increased in advancing liver fibrosis and declines with reduction in fibrosis in chronic hepatitis B.

Science.gov (United States)

Hui, Chee-Kin; Zhang, Hai-Ying; Lee, Nikki P; Chan, Weng; Yueng, Yui-Hung; Leung, Kar-Wai; Lu, Lei; Leung, Nancy; Lo, Chung-Mau; Fan, Sheung-Tat; Luk, John M; Xu, Aimin; Lam, Karen S; Kwong, Yok-Lam; Lau, George K K

2007-08-01

Despite the possible role of adiponectin in the pathogenesis of liver cirrhosis, few data have been collected from patients in different stages of liver fibrosis. We studied the role of adiponectin in 2 chronic hepatitis B (CHB)-patient cohorts. Serum adiponectin was quantified by enzyme-linked immunosorbent assay. One-hundred liver biopsy specimens from CHB patients with different stages of fibrosis and 38 paired liver biopsies from hepatitis B e antigen-positive patients randomized to lamivudine (n=15), pegylated interferon alfa-2a (n=15) or pegylated interferon alfa-2a plus lamivudine (n=8) therapy for 48 weeks were assessed. Serum adiponectin was detected at levels ranging over fourfold magnitude with advancing fibrosis stage and correlated positively with fibrosis stage [r=0.45, p<0.001]. CHB patients with stage 0-1 fibrosis had higher composition of high molecular weight (HMW) form of adiponectin when compared with CHB patients with liver cirrhosis [mean+/-SEM 51.2+/-2.1% vs. 40.9+/-1.7%, respectively, p=0.001]. After antiviral therapy, patients with fibrosis reduction had marked decline in serum adiponectin level and increase in HMW form of adiponectin [mean+/-SEM 43.5+/-1.2% vs. 37.0+/-3.0%, respectively, p=0.04]. Serum adiponectin may have a role in fibrosis progression in CHB infection. A marked decline in serum adiponectin after antiviral therapy is associated with fibrosis reduction.

Breath concentration of acetic acid vapour is elevated in patients with cystic fibrosis

Czech Academy of Sciences Publication Activity Database

Smith, D.; Sovová, Kristýna; Dryahina, Kseniya; Doušová, T.; Dřevínek, P.; Španěl, Patrik

2016-01-01

Roč. 10, č. 2 (2016), s. 021002 ISSN 1752-7155 R&D Projects: GA ČR(CZ) GA14-14534S Institutional support: RVO:61388955 Keywords : cystic fibrosis * SIFT-MS * acetic acid Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.318, year: 2016

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

Age effects on cortical thickness in young Down's syndrome subjects: a cross-sectional gender study

International Nuclear Information System (INIS)

Romano, Andrea; Moraschi, Marta; Cornia, Riccardo; Stella, Giacomo; Bozzao, Alessandro; Gagliardo, Olga; Chiacchiararelli, Laura; Iani, Cristina; Albertini, Giorgio; Pierallini, Alberto

2015-01-01

The aim of this study was to determine differences in the characteristic pattern of age-related cortical thinning in men and women with Down's syndrome (DS) by means of MRI and automatic cortical thickness measurements and a cross-sectional design, in a large cohort of young subjects. Eighty-four subjects with DS, 30 females (11-35 years, mean age ± SD = 22.8 ± 5.9) and 54 males (11-35 years, mean age ± SD = 21.5 ± 6.5), were examined using a 1.5-T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package. For all subjects participating in the study, the Pearson product-moment correlation coefficient between age and mean cortical thickness values has been evaluated. A significant negative correlation between cortical thickness and age was found in female DS subjects, predominantly in frontal and parietal lobes, bilaterally. In male DS subjects, a significant negative correlation between cortical thickness and age was found in the right fronto-temporal lobes and cingulate regions. Whole brain mean cortical thickness values were significantly negative correlated with age only in female DS subjects. Females with Down's syndrome showed a strong correlation between cortical thickness and age, already in early age. We suggest that the cognitive impairment due to hormonal deficit in the postmenopausal period could be emphasized by the early structural decline of gray matter in female DS subjects. (orig.)

Age effects on cortical thickness in young Down's syndrome subjects: a cross-sectional gender study

Energy Technology Data Exchange (ETDEWEB)

Romano, Andrea; Moraschi, Marta [San Raffaele Foundation Rome, Rehabilitation Facility Ceglie Messapica, Rome (Italy); Cornia, Riccardo; Stella, Giacomo [University of Modena and Reggio Emilia, Department of Education and Human Sciences, Emilia-Romagna (Italy); Bozzao, Alessandro; Gagliardo, Olga [University Sapienza, NESMOS, Department of Neuroradiology, S. Andrea Hospital, Rome (Italy); Chiacchiararelli, Laura [University Sapienza, Department of Medical Physics, S. Andrea Hospital, Rome (Italy); Iani, Cristina [University of Modena and Reggio Emilia, Department of Communication and Economy, Emilia-Romagna (Italy); Albertini, Giorgio [IRCSS San Raffaele Pisana, Department of Paediatrics, Rome (Italy); Pierallini, Alberto [IRCSS San Raffaele Pisana, Department of Radiology, Rome (Italy)

2015-04-01

The aim of this study was to determine differences in the characteristic pattern of age-related cortical thinning in men and women with Down's syndrome (DS) by means of MRI and automatic cortical thickness measurements and a cross-sectional design, in a large cohort of young subjects. Eighty-four subjects with DS, 30 females (11-35 years, mean age ± SD = 22.8 ± 5.9) and 54 males (11-35 years, mean age ± SD = 21.5 ± 6.5), were examined using a 1.5-T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package. For all subjects participating in the study, the Pearson product-moment correlation coefficient between age and mean cortical thickness values has been evaluated. A significant negative correlation between cortical thickness and age was found in female DS subjects, predominantly in frontal and parietal lobes, bilaterally. In male DS subjects, a significant negative correlation between cortical thickness and age was found in the right fronto-temporal lobes and cingulate regions. Whole brain mean cortical thickness values were significantly negative correlated with age only in female DS subjects. Females with Down's syndrome showed a strong correlation between cortical thickness and age, already in early age. We suggest that the cognitive impairment due to hormonal deficit in the postmenopausal period could be emphasized by the early structural decline of gray matter in female DS subjects. (orig.)

Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

International Nuclear Information System (INIS)

Spino, M.; Chai, R.P.; Isles, A.F.; Balfe, J.W.; Brown, R.G.; Thiessen, J.J.; MacLeod, S.M.

1985-01-01

A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and 125 I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion

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

Science.gov (United States)

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

2018-06-01

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

Oral White Lesions: Presentation and Comparison of Oral Submucous Fibrosis with Other Lesions

International Nuclear Information System (INIS)

Maqsood, A.; Aman, N.

2013-01-01

Objective: To compare oral submucous fibrosis with other white oral lesions for presentation and associated factors. Study Design: Cross-sectional study. Place and Duration of Study: The Departments of Oral Medicine and Oral and Maxillofacial Surgery, Dr. Ishrat-ul-Ibad Institute of Oral Health Sciences (DIKIOHS), Karachi, from May 2008 to May 2009. Methodology: Patients presenting with oral white lesions were selected by consecutive non-purposive sampling and clinico-demographic data was collected. For patients with oral submucous fibrosis (OSF), additional information like duration of habits, maximal incisal opening (MIO), presence of any other associated lesion were noted. OSF was compared with other white lesions for any association between characteristic of subjects. Chi-square and independent t-tests for determining the statistical significance at p < 0.05. Results: OSF was present in 59.6% (n = 106) of the 178 patients; other white lesions were 40.4% (n = 72). The mean age of patients with OSF was 34 +- 12.7 years and 45.81 +- 16.2 years in patients with other white lesions, (p < 0.0001). Items containing areca nut were consumed more by patients with OSF, with a significant (p < 0.0001) compared to patients with other white lesions. Conclusion: OSF was the predominant white lesion in patients examined at DIKIOHS. Areca nut was found to be chewed more by patients with OSF and still longer by patients with SCC. (author)

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.

Non-Invasive Evaluation of Cystic Fibrosis Related Liver Disease in Adults with ARFI, Transient Elastography and Different Fibrosis Scores

OpenAIRE

Karlas, Thomas; Neuschulz, Marie; Oltmanns, Annett; Güttler, Andrea; Petroff, David; Wirtz, Hubert; Mainz, Jochen G.; Mössner, Joachim; Berg, Thomas; Tröltzsch, Michael; Keim, Volker; Wiegand, Johannes

2012-01-01

BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is present in up to 30% of cystic fibrosis patients and can result in progressive liver failure. Diagnosis of CFLD is challenging. Non-invasive methods for staging of liver fibrosis display an interesting diagnostic approach for CFLD detection. AIM: We evaluated transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and fibrosis indices for CFLD detection. METHODS: TE and ARFI were performed in 55 adult CF patient...

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

Science.gov (United States)

Batman, Cosar; Ozdamar, Yasemin

2010-01-01

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

Nanoparticles for the treatment of liver fibrosis

Directory of Open Access Journals (Sweden)

Poilil Surendran S

2017-09-01

Full Text Available Suchithra Poilil Surendran, Reju George Thomas, Myeong Ju Moon, Yong Yeon Jeong Department of Radiology, BioMolecular Theranostics (BiT Lab, Chonnam National University Medical School, Chonnam National University Hwasun Hospital (CNUHH, South Korea Abstract: Chronic liver diseases represent a global health problem due to their high prevalence worldwide and the limited available curative treatment options. They can result from various causes, both infectious and noninfectious diseases. The application of nanoparticle (NP systems has emerged as a rapidly evolving area of interest for the safe delivery of various drugs and nucleic acids for chronic liver diseases. This review presents the pathogenesis, diagnosis and the emerging nanoparticulate systems used in the treatment of chronic liver diseases caused by liver fibrosis. Activated hepatic stellate cell (HSC is considered to be the main mechanism for liver fibrosis. Ultrasonography and magnetic resonance imaging techniques are widely used noninvasive diagnostic methods for hepatic fibrosis. A variety of nanoparticulate systems are mainly focused on targeting HSC in the treatment of hepatic fibrosis. As early liver fibrosis is reversible by current NP therapy, it is being studied in preclinical as well as clinical trials. Among various nanoparticulate systems, inorganic NPs, liposomes and nanomicelles have been widely studied due to their distinct properties to deliver drugs as well as other therapeutic moieties. Liposomal NPs in clinical trials is considered to be a milestone in the treatment of hepatic fibrosis. Currently, NP therapy for liver fibrosis is updating fast, and hopefully, it can be the future remedy for liver fibrosis. Keywords: liver fibrosis, inorganic nanoparticles, liposomes, micelles

Serum Iron and Haemoglobin Estimation in Oral Submucous Fibrosis and Iron Deficiency Anaemia: A Diagnostic Approach.

Science.gov (United States)

Bhardwaj, Divya; Dinkar, Ajit D; Satoskar, Sujata K; Desai, Sapna Raut

2016-12-01

Oral Submucous Fibrosis (OSMF) is a premalignant condition with potential malignant behaviour characterized by juxta-epithelial fibrosis of the oral cavity. In the process of collagen synthesis, iron gets utilized, by the hydroxylation of proline and lysine, leading to decreased serum iron levels. The trace element like iron is receiving much attention in the detection of oral cancer and precancerous condition like OSMF as it was found to be significantly altered in these conditions. The aim of this study was to compare the haemoglobin and serum iron values of OSMF subjects with that of iron deficiency anaemia subjects. Total of 120 subjects were included, 40 subjects with the OSMF, 40 with the iron deficiency anemia without tobacco chewing habit, 40 healthy control subjects without OSMF and iron deficiency anaemia. A total of 5ml of venous blood was withdrawn from all the subjects and serum iron and haemoglobin levels were estimated for all the subjects. Estimation of iron was done using Ferrozine method and haemoglobin by Sahli's method. The statistical method applied were Kruskal Wallis, Mann Whitney and Pearson correlation coefficient test. There was a statistically significant difference in serum iron and haemoglobin level in all three groups (pauxillary test in assessment of prognosis of the disease.

ASSOCIATION OF NUTRITIONAL STATUS WITH LUNG FUNCTION AND MORBIDITY IN CHILDREN AND ADOLESCENTS WITH CYSTIC FIBROSIS: A 36-MONTH COHORT STUDY.

Science.gov (United States)

Hauschild, Daniela Barbieri; Rosa, Anauã Franco; Ventura, Julia Carvalho; Barbosa, Eliana; Moreira, Emília Addison Machado; Ludwig Neto, Norberto; Moreno, Yara Maria Franco

2018-01-01

To evaluate the association between nutritional status, lung function and morbidity in a 36-month cohort in children and adolescents with cystic fibrosis. Prospective cohort of children and adolescents with cystic fibrosis aged 1-15 years. At the baseline, the nutritional status was determined by weight-for-height and body mass index-for-age for children 36 months. Those classified bellow the 50th percentile had a RR of 4.61 (95%CI 0.89; 23.81) to present the same outcome. Nutritional status was not a risk factor for morbidity in this cohort. Nutritional deficit was associated with impaired lung function, but not with morbidity in children and adolescents with cystic fibrosis.

Nutritional status and body fat distribution in children and adolescentes with Cystic Fibrosis.

Science.gov (United States)

Chaves, Célia Regina Moutinho de Miranda; Cunha, Ana Lúcia Pereira da; Costa, Ana Carolina da; Costa, Roseli de Souza Santos da; Lacerda, Speranza Vieira

2015-11-01

assessing the nutritional status and body fat distribution in children and adolescents with cystic fibrosis. Fifty-six (56) 8-18 year old patients were assessed for fat distribution by dual energy X-ray absorptiometry, for nutritional status by height/age, and for body mass index to age and dietary intake by 24-hour dietary recall. Approximately 50% of the sample showed adequate nutritional status. Most of it showed inadequate caloric and lipid intake. BMI/age was the nutritional indicator that best showed the increased percentage of trunk fat, android/gynecoidratio and trunk fat/total fat ratio. Patients with Pancreatic Insufficiency and eutrophic individuals showed higher median android/gynecoidratio. Increased abdominal adiposity was evidenced by DXA. The BMI did not identify decreased lean body mass. However, when body mass was high, it was significant for abdominal adiposity. The anthropometric assessment of patients with cystic fibrosis should be associated with body composition and body fat distribution to obtain an earlier malnutrition and cardiometabolic risk factor diagnosis.

Renal microvascular disease in an aging population: a reversible process?

Science.gov (United States)

Futrakul, Narisa; Futrakul, Prasit

2008-01-01

Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process.

Cat and dog exposure and respiratory morbidities in cystic fibrosis.

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Morrow, Christopher B; Raraigh, Karen S; Green, Deanna M; Blackman, Scott M; Cutting, Garry R; Collaco, Joseph M

2014-10-01

To understand the triggers that may impact respiratory health in cystic fibrosis (CF), including the effects of pets, because environmental factors contribute to one-half of the variation in lung function in patients with CF. A total of 703 subjects with CF were recruited through the US CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of cats and dogs in households with a child with CF. Questionnaires, chart review, and US CF Foundation Patient Registry data were used to track respiratory and infection outcomes. Within the sample, 47% of subjects reported owning a dog, and 28% reported owning a cat. After adjustment for demographic factors, dog ownership was not associated with any adverse clinical outcomes, and cat ownership was associated an increased risk in developing nasal polyps (aOR 1.66; P = .024) compared with noncat owners. Subjects who owned both cats and dogs were twice as likely to report wheezing compared with other subjects (aOR: 2.01; P = .009). There were no differences in prevalence and age of acquisition for the common CF respiratory pathogens Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus between cat/dog owners and noncat/dog owners. Cat ownership was associated with a greater frequency of developing nasal polyps and combined cat-dog ownership was associated with a greater rate of wheezing. Prospective studies are needed to confirm these associations and the potential psychosocial benefits of cat and/or dog ownership. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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

2017-09-15

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

Transient and 2-Dimensional Shear-Wave Elastography Provide Comparable Assessment of Alcoholic Liver Fibrosis and Cirrhosis.

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Thiele, Maja; Detlefsen, Sönke; Sevelsted Møller, Linda; Madsen, Bjørn Stæhr; Fuglsang Hansen, Janne; Fialla, Annette Dam; Trebicka, Jonel; Krag, Aleksander

2016-01-01

Alcohol abuse causes half of all deaths from cirrhosis in the West, but few tools are available for noninvasive diagnosis of alcoholic liver disease. We evaluated 2 elastography techniques for diagnosis of alcoholic fibrosis and cirrhosis; liver biopsy with Ishak score and collagen-proportionate area were used as reference. We performed a prospective study of 199 consecutive patients with ongoing or prior alcohol abuse, but without known liver disease. One group of patients had a high pretest probability of cirrhosis because they were identified at hospital liver clinics (in Southern Denmark). The second, lower-risk group, was recruited from municipal alcohol rehabilitation centers and the Danish national public health portal. All subjects underwent same-day transient elastography (FibroScan), 2-dimensional shear wave elastography (Supersonic Aixplorer), and liver biopsy after an overnight fast. Transient elastography and 2-dimensional shear wave elastography identified subjects in each group with significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) with high accuracy (area under the curve ≥0.92). There was no difference in diagnostic accuracy between techniques. The cutoff values for optimal identification of significant fibrosis by transient elastography and 2-dimensional shear wave elastography were 9.6 kPa and 10.2 kPa, and for cirrhosis 19.7 kPa and 16.4 kPa. Negative predictive values were high for both groups, but the positive predictive value for cirrhosis was >66% in the high-risk group vs approximately 50% in the low-risk group. Evidence of alcohol-induced damage to cholangiocytes, but not ongoing alcohol abuse, affected liver stiffness. The collagen-proportionate area correlated with Ishak grades and accurately identified individuals with significant fibrosis and cirrhosis. In a prospective study of individuals at risk for liver fibrosis due to alcohol consumption, we found elastography to be an excellent tool for diagnosing liver

Long-Term Follow-Up in a Girl with Cystic Fibrosis and Diabetes Since the First Year of Life.

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Fattorusso, Valentina; Casale, Alida; Raia, Valeria; Mozzillo, Enza; Franzese, Adriana

2017-10-01

Diabetes mellitus is the most common comorbidity in cystic fibrosis (CF). Recently, more attention has been paid to early glucose metabolism derangements (GMDs). The subject of this report is a female patient, affected by CF since 3 months of age. She presented with intermittent diabetes during early childhood. At the age of 10 years, oral glucose tolerance test (OGTT) was performed and showed glucose intolerance (IGT) status; glargine insulin therapy was started. At the age of 13 years, CF-related diabetes with fasting hyperglycemia occurred, so rapid insulin at meals was added. During the following year, clinical and nutritional status improved. Stable clinical conditions were observed in the following 3 years. This is the first case of very long-term follow-up concerning a CF patient with GMDs. Our case confirms the importance of paying attention to early GMDs in very young CF patients and seems to suggest that earlier therapy could ameliorate CF natural history.

Association of High-Dose Ibuprofen Use, Lung Function Decline, and Long-Term Survival in Children with Cystic Fibrosis.

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Konstan, Michael W; VanDevanter, Donald R; Sawicki, Gregory S; Pasta, David J; Foreman, Aimee J; Neiman, Evgueni A; Morgan, Wayne J

2018-04-01

Cystic fibrosis deaths result primarily from lung function loss, so chronic respiratory therapies, intended to preserve lung function, are cornerstones of cystic fibrosis care. Although treatment-associated reduction in rate of lung function loss should ultimately improve cystic fibrosis survival, no such relationship has been described for any chronic cystic fibrosis therapy. In part, this is because the ages of most rapid lung function decline-early adolescence-precede the median age of cystic fibrosis deaths by more than a decade. To study associations of high-dose ibuprofen treatment with the rate of forced expiratory volume in 1 second decline and mortality among children followed in the Epidemiologic Study of Cystic Fibrosis and subsequently in the U.S. Cystic Fibrosis Foundation Patient Registry. We performed a matched cohort study using data from Epidemiologic Study of Cystic Fibrosis. Exposure was defined as high-dose ibuprofen use reported at ≥80% of encounters over 2 years. Unexposed children were matched to exposed children 5:1 using propensity scores on the basis of demographic, clinical, and treatment covariates. The rate of decline of percent predicted forced expiratory volume in 1 second during the 2-year follow-up period was estimated by mixed-effects modeling with random slopes and intercepts. Survival over 16 follow-up years in the U.S. Cystic Fibrosis Foundation Patient Registry was compared between treatment groups by using proportional hazards modeling controlling for matching and covariates. We included 775 high-dose ibuprofen users and 3,665 nonusers who were well matched on demographic, clinical, and treatment variables. High-dose ibuprofen users declined on average 1.10 percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 0.51, 1.69) during the 2-year treatment period, whereas nonusers declined at a rate of 1.76% percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 1.48, 2

Liver Fibrosis: Current Principles of Diagnosis

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A.K. Duda

2014-09-01

Full Text Available Liver fibrosis — a natural consequence of almost all liver diseases of any origin. We are faced with a number of standard stereotype processes that take place in the liver tissue. Mostly it is the processes of chronic inflammation, which oppose the processes of liver tissue regeneration. The basis of imbalance between the processes of fibrosis and regeneration is an accumulation of extracellular matrix. Liver fibrosis in its development leads to liver cirrhosis, hepatocellular carcinoma, and the increase in morbidity rate is observed worldwide. Furthermore, the process is genetically determined, but modifiable factors play an important role in the progression of this disease. Current data indicate the possibility of reversible liver fibrosis.

The impact of physical activity on endothelial function in middle-aged and elderly subjects: the Ikaria study.

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Siasos, Gerasimos; Chrysohoou, Christina; Tousoulis, Dimitris; Oikonomou, Evangelos; Panagiotakos, Demosthenes; Zaromitidou, Marina; Zisimos, Konstantinos; Marinos, Georgios; Mazaris, Savvas; Kampaksis, Manolis; Papavassiliou, Athanasios G; Pitsavos, Christos; Stefanadis, Christodoulos

2013-01-01

Exercise training and physical activity (PA) have substantial vascular and cardiac health benefits. Ikaria Island has been recognised as having one of the highest longevity rates worldwide and a high percentage of healthy ageing. We examined the relationship between endothelial function and levels of habitual PA to evaluate the factors related to healthy ageing in this population. The study was conducted on a subgroup population of the IKARIA study consisting of 185 middle-aged (40-65 years) and 142 elderly subjects (66-91 years). Endothelial function was evaluated by ultrasound measurement of flow-mediated dilatation (FMD). PA was evaluated using the shortened version of the self-reported International Physical Activity Questionnaire (IPAQ). Subjects in the low PA group (physically inactive and the rest as active. In the overall study population FMD was inversely associated with age (r=-0.24, pphysically active had higher FMD compared with the physically inactive. Physically active subjects in the middle-aged group showed higher FMD compared with the physically active elderly (p=0.008). However, there was no difference in FMD values between middle-aged inactive subjects and the elderly physically active (p=NS). The present study revealed that increased PA was associated with improved endothelial function in middle-aged subjects and that PA in elderly subjects can ameliorate the devastating effects of ageing on arterial wall properties.

How avoidant attachment influences subjective well-being: an investigation about the age and gender differences.

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Li, Tianyuan; Fung, Helene H

2014-01-01

Intimate relationship is a significant factor that influences older adults' subjective well-being. Avoidant attachment reflects a basic working model regarding interpersonal relationships. The current study aims to test how age and gender moderate the effect of avoidant attachment to spouse on subjective well-being. Fifty-six married couples aged from 20 to 79 years in Hong Kong were recruited for the study. Their avoidant attachment to spouse and subjective well-being were measured by questionnaires. In general, avoidant attachment to spouse was found to undermine subjective well-being. More importantly, age significantly moderated the negative association between avoidant attachment and subjective well-being, but the direction of the moderating effect was opposite for husbands and wives. Compared with their younger counterparts, the detrimental effect of avoidant attachment on subjective well-being was weaker for older wives but stronger for older husbands. The results suggest that marital relationship may play different roles in different life stages for the two genders. In later adulthood, males may become more dependent on the marital relationship to maintain subjective well-being, whereas females can be relatively independent.

Respiratory infection rates differ between geographically distant paediatric cystic fibrosis cohorts

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Kathryn A. Ramsey

2016-09-01

Full Text Available Respiratory infections are a major cause of pulmonary decline in children with cystic fibrosis (CF. We compared the prevalence of infection in early life at geographically distant CF treatment centres participating in the same surveillance programme in Australia. Lower airway microbiology, inflammation and structural lung disease at annual review were evaluated for 260 children 0–8 years old with CF at 1032 visits to CF treatment centres in Melbourne or Perth. Melbourne patients were more likely to be culture-positive for common respiratory pathogens at all age groups (odds ratio (OR 1.85, 95% CI 1.33–2.58. Subjects 5 years old. Patients at both centres had a similar rate of hospitalisations and prescribed antibiotics. No procedural differences were identified that could explain the disparity between pathogen prevalence. Geographical differences in early acquisition of infection may contribute to variability in outcomes between CF centres.

Longitudinal research on subjective aging, health, and longevity : Current evidence and new directions for research

NARCIS (Netherlands)

Westerhof, Gerben J.; Wurm, Susanne

2015-01-01

In this chapter, we carry out a narrative review of the longitudinal impact of subjective aging on health and survival. We have a specifi c focus on the different pathways which can explain the relation of subjective aging to health and survival. We focus on the three most common conceptualizations

Bilateral versus single lung transplant for idiopathic pulmonary fibrosis.

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Lehmann, Sven; Uhlemann, Madlen; Leontyev, Sergey; Seeburger, Joerg; Garbade, Jens; Merk, Denis R; Bittner, Hartmuth B; Mohr, Friedrich W

2014-10-01

It is unknown if uni- or bilateral lung transplant is best for treatment of usual idiopathic pulmonary fibrosis. We reviewed our single-center experience comparing both treatments. Between 2002 and 2011, one hundred thirty-eight patients at our institution underwent a lung transplant. Of these, 58 patients presented with idiopathic pulmonary fibrosis (56.9%) and were the focus of this study. Thirty-nine patients received a single lung transplant and 19 patients a bilateral sequential lung transplant. The mean patient age was 54 ± 10 years, and 69% were male. The intraoperative course was uneventful, save for 7 patients who needed extracorporeal membrane oxygenation support. Three patients had respiratory failure before the lung transplant that required mechanical ventilation and was supported by extracorporeal membrane oxygenation. Elevated pulmonary artery pressure > 40 mm Hg was identified as an independent predictor of early mortality by uni- and multivariate analysis (P = .01; OR 9.7). Using a Cox regression analysis, postoperative extracorporeal membrane oxyge-nation therapy (P = .01; OR 10.2) and the need for > 10 red blood cell concentrate during the first 72 hours after lung transplant (P = .01; OR 5.6) were independent predictors of long-term survival. Actuarial survival at 1 and 5 years was 65.6% and 55.3%, with no significant between-group differences (70.6% and 54.3%). Lung transplant is a safe and curative treatment for idiopathic pulmonary fibrosis. According to our results, unilateral lung transplant for idiopathic pulmonary fibrosis is an alternative to bilateral lung transplant and may affect the allocation process.

Association between subjective actual sleep duration, subjective sleep need, age, body mass index, and gender in a large sample of young adults.

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Kalak, Nadeem; Brand, Serge; Beck, Johannes; Holsboer-Trachsler, Edith; Wollmer, M Axel

2015-01-01

Poor sleep is a major health concern, and there is evidence that young adults are at increased risk of suffering from poor sleep. There is also evidence that sleep duration can vary as a function of gender and body mass index (BMI). We sought to replicate these findings in a large sample of young adults, and also tested the hypothesis that a smaller gap between subjective sleep duration and subjective sleep need is associated with a greater feeling of being restored. A total of 2,929 university students (mean age 23.24±3.13 years, 69.1% female) took part in an Internet-based survey. They answered questions related to demographics and subjective sleep patterns. We found no gender differences in subjective sleep duration, subjective sleep need, BMI, age, or feeling of being restored. Nonlinear associations were observed between subjective sleep duration, BMI, and feeling of being restored. Moreover, a larger discrepancy between subjective actual sleep duration and subjective sleep need was associated with a lower feeling of being restored. The present pattern of results from a large sample of young adults suggests that males and females do not differ with respect to subjective sleep duration, BMI, or feeling of being restored. Moreover, nonlinear correlations seemed to provide a more accurate reflection of the relationship between subjective sleep and demographic variables.

IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD - a pilot study.

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Hagström, Hannes; Stål, Per; Hultcrantz, Rolf; Brismar, Kerstin; Ansurudeen, Ishrath

2017-12-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. Advanced fibrosis (stage 3-4) is the most robust marker for future mortality, but diagnosis requires liver biopsy. Current non-invasive scoring systems aimed to identify advanced fibrosis are imperfect. Insulin-like growth factor I (IGF-I) and its binding protein IGFBP-1 are liver derived proteins, that are involved in various liver disorders. The aim of this study was to examine the possible association between advanced fibrosis and IGF-I and IGFBP-1 in NAFLD. Fasting blood samples were obtained from 52 patients diagnosed with NAFLD by liver biopsy. Total IGF-I and IGFBP-1 concentrations were determined in serum by in-house radio-immuno-assays. IGF-I levels were age-standardized (IGF-SD). A logistic regression model was used to investigate the association of IGF-SD and IGFBP-1 with advanced fibrosis (stage 3-4). Patients with advanced fibrosis (stage 3-4 vs. 0-2) had lower IGF-SD (-1.17 vs. 0.11, p = .01) and higher mean levels of IGFBP-1 (29.9 vs. 18.8 µg/l, p = .02). IGFBP-1 was associated with presence of advanced fibrosis (OR 1.04 per unit increase, 95%CI 1.0-1.07, p = .05), while IGF-1 was negatively associated with advanced fibrosis (OR 0.63 per standard deviation, 95%CI 0.44-0.92, p = .02). This pilot study suggests an association between serum IGFBP-1 and IGF-I levels with advanced fibrosis in NAFLD patients. IGFBP1 and IGF-1 could be of interest as future biomarkers. Similar studies in larger cohorts are needed.

Defects in MAP1S-mediated autophagy turnover of fibronectin cause renal fibrosis.

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Xu, Guibin; Yue, Fei; Huang, Hai; He, Yongzhong; Li, Xun; Zhao, Haibo; Su, Zhengming; Jiang, Xianhan; Li, Wenjiao; Zou, Jing; Chen, Qi; Liu, Leyuan

2016-05-01

Excessive deposition of extracellular matrix proteins in renal tissues causes renal fibrosis and renal function failure. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles. MAP1S is an autophagy activator and promotes the biogenesis and degradation of autophagosomes. Previously, we reported that MAP1S suppresses hepatocellular carcinogenesis in a mouse model and predicts a better prognosis in patients suffering from clear cell renal cell carcinomas. Furthermore, we have characterized that MAP1S enhances the turnover of fibronectin, and mice overexpressing LC3 but with MAP1S deleted accumulate fibronectin and develop liver fibrosis because of the synergistic impact of LC3-induced over-synthesis of fibronectin and MAP1S depletion-caused impairment of fibronectin degradation. Here we show that a suppression of MAP1S in renal cells caused an impairment of autophagy clearance of fibronectin and an activation of pyroptosis. Depletion of MAP1S in mice leads to an accumulation of fibrosis-related proteins and the development of renal fibrosis in aged mice. The levels of MAP1S were dramatically reduced and levels of fibronectin were greatly elevated in renal fibrotic tissues from patients diagnosed as renal atrophy and renal failure. Therefore, MAP1S deficiency may cause the accumulation of fibronectin and the development of renal fibrosis.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Otorhinolaryngologic manifestations of cystic fibrosis: literature review

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Carvalho, Carolina Pimenta

2008-12-01

Full Text Available Introduction: Cystic Fibrosis is the most common recessive autosomic genetic disease among Caucasians. It's caused by mutations in the gene that decodes regulatory protein for transmembrane conductance, resulting in defective transport of chlorine. Objective: Review the literature about Cystic Fibrosis, with emphasis on otorhinolaryngologic manifestations. Method: The online Pub Med databases were researched and we applied the following search terms Fibrosis Cystic and Sinusitis, and Mucoviscidosis and Sinusitis. Conclusions: Although it is not the main cause of death, the otorhinolaryngologic manifestations of the Cystic Fibrosis bring important morbidity to these patients.

Viral infection drives tissue fibrosis in vitro

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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.

Health-related quality of life of Spanish children with cystic fibrosis.

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Groeneveld, Iris F; Sosa, Elena S; Pérez, Margarita; Fiuza-Luces, Carmen; Gonzalez-Saiz, Laura; Gallardo, Cristian; López-Mojares, Luis M; Ruiz, Jonatan R; Lucia, Alejandro

2012-12-01

To investigate (1) the contributions of sex, age, nutritional status- and physical-fitness-related variables on health-related quality of life (HRQOL) in Spanish children with cystic fibrosis, and (2) the agreement on HRQOL between children and their parents. In 28 children aged 6-17 years, body mass index percentile, percentage body fat, physical activity, pulmonary function, cardiorespiratory fitness, functional mobility, and dynamic muscle strength were determined using objective measures. HRQOL was measured using the revised version of the cystic fibrosis questionnaire. Simple and multiple linear regression analyses were performed to determine the variables associated with HRQOL. To assess the agreement on HRQOL between children and parents, intra-class correlation coefficients (ICCs) were calculated. Girls reported worse emotional functioning, a higher treatment burden, and more respiratory problems than boys. Greater functional mobility appeared associated with a less favourable body image and more eating disturbances. Agreement on HRQOL between children and parents was good to excellent, except for the domain of treatment burden. Sex and age were stronger predictors of HRQOL than nutritional status- or physical-fitness-related variables. Children reported a lower treatment burden than their parents perceived them to have.

Quantification and significance of diffuse myocardial fibrosis and diastolic dysfunction in childhood hypertrophic cardiomyopathy.

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Hussain, Tarique; Dragulescu, Andreea; Benson, Lee; Yoo, Shi-Joon; Meng, Howard; Windram, Jonathan; Wong, Derek; Greiser, Andreas; Friedberg, Mark; Mertens, Luc; Seed, Michael; Redington, Andrew; Grosse-Wortmann, Lars

2015-06-01

The purpose of this study was to evaluate the presence of diffuse myocardial fibrosis in children and adolescents with hypertrophic cardiomyopathy (HCM) and to assess associations with echocardiographic and clinical parameters of disease. While a common end point in adults with HCM, it is unclear whether diffuse myocardial fibrosis occurs early in the disease. Cardiac magnetic resonance (CMR) estimation of myocardial post-contrast longitudinal relaxation time (T1) is an increasingly used method to estimate diffuse fibrosis. T1 measurements were taken using standard multi-breath-hold spoiled gradient echo phase-sensitive inversion-recovery CMR before and 15 min after the injection of gadolinium. The tissue-blood partition coefficient was calculated as a function of the ratio of T1 change of myocardium compared with blood. An echocardiogram and blood brain natriuretic peptide (BNP) levels were obtained on the day of the CMR. Twelve controls (mean age 12.8 years; 7 male) and 28 patients with HCM (mean age 12.8 years; 21 male) participated. The partition coefficient for both septal (0.27 ± 0.17 vs. 0.13 ± 0.09; p = 0.03) and lateral walls (0.22 ± 0.09 vs. 0.07 ± 0.10; p 100 pg/ml) had raised lateral wall coefficients (0.27 ± 0.07 vs. 0.20 ± 0.07; p = 0.03), as did those with traditional risk factors for sudden death (0.27 ± 0.06 vs. 0.18 ± 0.08; p = 0.007). Diffuse fibrosis, measured by the partition coefficient technique, is demonstrable in children and adolescents with HCM. Markers of fibrosis show an association with symptoms and raised serum BNP. Further study of the prognostic implication of this technique in young patients with HCM is warranted.

Current Strategies for Quantitating Fibrosis in Liver Biopsy

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Yan Wang

2015-01-01

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

Clinical application of noninvasive diagnosis of liver fibrosis

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ZHU Chuanlong

2015-03-01

Full Text Available Hepatic fibrosis is the common outcome of chronic liver diseases of various causes. At present, liver biopsy is the “gold standard” for the diagnosis of liver fibrosis, but it has limitations and is invasive, which leads to the development of noninvasive assessment of liver fibrosis. The article mainly introduces the technology and application of noninvasive diagnosis of liver fibrosis from the aspects of clinical manifestation, serology, and radiology. It has pointed out the clinical value of these noninvasive diagnosis techniques, and it discusses the progress in clinical research and its limitations for noninvasive diagnosis of liver fibrosis.

Imaging findings in idiopathic pelvic fibrosis

International Nuclear Information System (INIS)

Wiesner, W.; Bongartz, G.; Stoffel, F.

2001-01-01

Two patients presented with ureteric obstruction, and voiding symptoms and constipation, respectively, and were examined by means of intravenous urography and computed tomography. One patient was additionally examined by means of MR tomography. After CT (performed in both patients) and MRT (performed in one patient) had shown a diffuse, contrast-enhancing, infiltrating process in the small pelvis with infiltration of adjacent organs and vessels, surgical biopsy proved the diagnosis of idopathic pelvic fibrosis. Extension of retroperitoneal fibrosis below the pelvic rim is very rare. Clinical symptoms of pelvic fibrosis are variable and imaging findings may lead to a broad list of differential diagnoses. We present two patients with idiopathic pelvic fibrosis and discuss radiological findings and differential diagnoses of this rare disease. (orig.)

Imaging findings in idiopathic pelvic fibrosis

Energy Technology Data Exchange (ETDEWEB)

Wiesner, W.; Bongartz, G. [Inst. of Diagnostic Radiology University Hospital Basel (Switzerland); Stoffel, F. [Inst. of Urology, University Hospital Basel (Switzerland)

2001-04-01

Two patients presented with ureteric obstruction, and voiding symptoms and constipation, respectively, and were examined by means of intravenous urography and computed tomography. One patient was additionally examined by means of MR tomography. After CT (performed in both patients) and MRT (performed in one patient) had shown a diffuse, contrast-enhancing, infiltrating process in the small pelvis with infiltration of adjacent organs and vessels, surgical biopsy proved the diagnosis of idopathic pelvic fibrosis. Extension of retroperitoneal fibrosis below the pelvic rim is very rare. Clinical symptoms of pelvic fibrosis are variable and imaging findings may lead to a broad list of differential diagnoses. We present two patients with idiopathic pelvic fibrosis and discuss radiological findings and differential diagnoses of this rare disease. (orig.)

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.

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.

Age identity and subjective well-being: A comparison of the United States and Germany

NARCIS (Netherlands)

Westerhof, G.J.; Barrett, A.E.

2005-01-01

Objectives. This article investigates the theoretical and empirical relationship between age identity and subjective well-being (SWB) in a cross-national context. Feeling younger than one's actual age is considered a self-enhancing illusion that contributes to SWB even beyond factors predicting age

Factors Promoting Development of Fibrosis in Crohn’s Disease

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Gerhard Rogler

2017-07-01

Full Text Available The concepts on the pathophysiology of intestinal fibrosis in Crohn’s disease (CD have changed in recent years. Some years ago fibrosis was regarded to be a consequence of long-standing inflammation with subsequent destruction of the gut wall matrix followed by scar formation and collagen deposition. Fibrosis in CD patients appeared to be an irreversible process that could hardly be influenced. Therefore, the main target in CD therapy was to control inflammation to avoid fibrosis development. Many of these assumptions seem to be only partially true. Inflammation may be a necessary prerequisite for the initiation of fibrosis. However, when the pathophysiologic processes that lead to fibrosis in CD patients have been initiated fibrosis development may be independent of inflammation and may continue even when inflammation is under good medical control. Fibrosis in CD also may be reversible. After strictureplasty local collagen deposits decrease or even disappear. With new animal models for intestinal fibrosis on the horizon, we need to spend more efforts on understanding the factors influencing fibrosis in CD patients to finally find specific therapies. In this context, it will be as important to find markers and quantitative imaging tools to have reliable endpoints for clinical trials in fibrosing CD.

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.

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

Science.gov (United States)

Somaraju, Usha Rani; Solis-Moya, Arturo

2016-11-23

Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One

Serum hyaluronic acid as a marker of hepatic fibrosis

International Nuclear Information System (INIS)

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

2007-01-01

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

Recommendations for quality improvement in genetic testing for cystic fibrosis European Concerted Action on Cystic Fibrosis

NARCIS (Netherlands)

Dequeker, E; Cuppens, H; Dodge, J; Estivill, [No Value; Goossens, M; Pignatti, PF; Scheffer, H; Schwartz, M; Schwarz, M; Tummler, B; Cassiman, JJ

These recommendations for quality improvement of cystic fibrosis genetic diagnostic testing provide general guidelines for the molecular genetic testing of cystic fibrosis in patients/individuals. General strategies for testing as well as guidelines for laboratory procedures, internal and external

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

Science.gov (United States)

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

2009-05-01

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

Association between cognitive impairment and eating habits in elderly Chinese subjects over 90 years of age.

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Gao, Lingyun; Dong, Birong; Hao, Qiu Kui; Ding, Xiang

2013-08-01

Eating habits may have a key influence on cognitive function, however, the relationship between dietary intake and cognitive impairment in the elderly Chinese population has not been explored. The present study investigated the association between cognitive impairment and eating habits in elderly Chinese subjects >90 years of age. This study comprised data from subjects included in the 2005 Project of Longevity and Ageing in Dujiangyan, China. Subjects were divided into two groups: cognitive impairment group and normal group. Sociodemographic and dietary habit data were collected and cognitive function was assessed in all subjects using the Mini-Mental State Examination. Data from 763 subjects (249 men, 514 women) were included. There was no statistically significant difference in eating habits between the two groups. Education level in the cognitive impairment group was significantly lower than in the normal group. Significant between-group differences were detected in factors relating to subjects' professions. Eating habits were not related to cognitive impairment in elderly Chinese people >90 years of age.

Modeling the mechanical properties of liver fibrosis in rats.

Science.gov (United States)

Zhu, Ying; Chen, Xin; Zhang, Xinyu; Chen, Siping; Shen, Yuanyuan; Song, Liang

2016-06-14

The progression of liver fibrosis changes the biomechanical properties of liver tissue. This study characterized and compared different liver fibrosis stages in rats in terms of viscoelasticity. Three viscoelastic models, the Voigt, Maxwell, and Zener models, were applied to experimental data from rheometer tests and then the elasticity and viscosity were estimated for each fibrosis stage. The study found that both elasticity and viscosity are correlated with the various stages of liver fibrosis. The study revealed that the Zener model is the optimal model for describing the mechanical properties of each fibrosis stage, but there is no significant difference between the Zener and Voigt models in their performance on liver fibrosis staging. Therefore the Voigt model can still be effectively used for liver fibrosis grading. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2004-08-01

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

Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening.

Science.gov (United States)

Stuart, Bridget D; Choi, Jungmin; Zaidi, Samir; Xing, Chao; Holohan, Brody; Chen, Rui; Choi, Mihwa; Dharwadkar, Pooja; Torres, Fernando; Girod, Carlos E; Weissler, Jonathan; Fitzgerald, John; Kershaw, Corey; Klesney-Tait, Julia; Mageto, Yolanda; Shay, Jerry W; Ji, Weizhen; Bilguvar, Kaya; Mane, Shrikant; Lifton, Richard P; Garcia, Christine Kim

2015-05-01

Idiopathic pulmonary fibrosis (IPF) is an age-related disease featuring progressive lung scarring. To elucidate the molecular basis of IPF, we performed exome sequencing of familial kindreds with pulmonary fibrosis. Gene burden analysis comparing 78 European cases and 2,816 controls implicated PARN, an exoribonuclease with no previous connection to telomere biology or disease, with five new heterozygous damaging mutations in unrelated cases and none in controls (P = 1.3 × 10(-8)); mutations were shared by all affected relatives (odds in favor of linkage = 4,096:1). RTEL1, an established locus for dyskeratosis congenita, harbored significantly more new damaging and missense variants at conserved residues in cases than in controls (P = 1.6 × 10(-6)). PARN and RTEL1 mutation carriers had shortened leukocyte telomere lengths, and we observed epigenetic inheritance of short telomeres in family members. Together, these genes explain ~7% of familial pulmonary fibrosis and strengthen the link between lung fibrosis and telomere dysfunction.

Computed tomography of cystic pancreatic fibrosis

International Nuclear Information System (INIS)

Brachlow, M.; Zaunbauer, W.; Haertel, M.

1984-01-01

The computer tomographic appearances of atrophic and lipomatous degeneration of the pancreas in cystic pancreatic fibrosis are described. CT exploration of the pancreas in recommended, particularly in differential diagnostic aspects of cystic fibrosis. (orig.) [de

Oral calorie supplements for cystic fibrosis.

Science.gov (United States)

Smyth, Rosalind L; Rayner, Oli

2017-05-04

concerns surrounding allocation concealment. There were no significant differences between people receiving supplements or dietary advice alone for change in weight, height, body mass index, z score or other indices of nutrition or growth. Changes in weight (kg) at three, six and 12 months respectively were: mean difference (MD) 0.32 (95% confidence interval (CI) -0.09 to 0.72); MD 0.47 (95% CI -0.07 to 1.02 ); and MD 0.16 (-0.68 to 1.00). Total calorie intake was greater in people taking supplements at 12 months, MD 265.70 (95% CI 42.94 to 488.46). There were no significant differences between the groups for anthropometric measures of body composition, lung function, gastro-intestinal adverse effects or activity levels. Moderate quality evidence exists for the outcomes of changes in weight and height and low quality evidence exists for the outcomes of change in total calories, total fat and total protein intake as results are applicable only to children between the ages of 2 and 15 years and many post-treatment diet diaries were not returned. Evidence for the rate of adverse events in the treatment groups was extremely limited and judged to be of very low quality AUTHORS' CONCLUSIONS: Oral calorie supplements do not confer any additional benefit in the nutritional management of moderately malnourished children with cystic fibrosis over and above the use of dietary advice and monitoring alone. While nutritional supplements may be used, they should not be regarded as essential. Further randomised controlled trials are needed to establish the role of short-term oral protein energy supplements in people with cystic fibrosis and acute weight loss and also for the long-term nutritional management of adults with cystic fibrosis or advanced lung disease, or both.

Effect of Ganfukang on liver function and serum hepatic fibrosis markers levels in SD rats with experimental hepatic fibrosis

International Nuclear Information System (INIS)

Che Ying; Wang Shanju; Xu Tingting; Jiang Miaona; Jia Yujie

2004-01-01

Objective: To observe the effect of Ganfukang on liver function and serum hepatic fibrosis markers levels in SD rats with experimental hepatic fibrosis. Methods: SD rat models of liver fibrosis was induced by CCl 4 (n=57). Liver function (GPT, GOT) and serum hepatic fibrosis markers levels (HA, LN, C-IV, PC-III, with RIA) were tested in these models and 10 control rats. Eleven model rats were left untreated, the others were treated with Ganfukang of different concentrations and the above hepatic parameters were again determined after completion of treatment. Results: Lever function was much deteriorated and serum markers levels significantly increased in the model rats (vs controls, P<0.01). After treatment with Ganfukang, the improvement was significant (vs untreated models, P<0.01). Conclusion: Ganfukang is of definite therapeutic value for experimental hepatic fibrosis in rat models. (authors)

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

Directory of Open Access Journals (Sweden)

Seung Up Kim

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

The age and subjective well-being paradox revisited:A multidimensional perspective

Directory of Open Access Journals (Sweden)

Thomas Hansen

2012-11-01

Full Text Available This study re-examines the much-discussed paradox that although aging is associated with declines in many life domains, overall subjective well-being does not appear to decline sharply with age. We use data from two waves of the Norwegian NorLAG study (age 40-85, n=3,750 and examine age differences in change in well-being outcomes (life satisfaction, positive affect, negative affect, and depression and factors that may account for age variations in such change. Outcomes show stability well into older age, but negative changes in advanced age, cross-sectionally or longitudinally. Life satisfaction and negative affect are adversely related to older age longitudinally, whereas positive affect and depression are adversely related to older age in the cross-section. Results are similar for men and women. Loss of health and partner are the main causes of declining well-being in older age. Findings suggest qualifications to the “well-being paradox”, e.g.: only some dimensions of SWB remain stable, while others decline; across dimensions SWB change is more negative in old-old than in young-old age.

Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects.

Science.gov (United States)

Högman, M; Thornadtsson, A; Liv, P; Hua-Huy, T; Dinh-Xuan, A T; Tufvesson, E; Dressel, H; Janson, C; Koskela, K; Oksa, P; Sauni, R; Uitti, J; Moilanen, E; Lehtimäki, L

2017-09-13

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (F E NO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (C A NO), airway flux (J aw NO), airway diffusing capacity (D aw NO) and airway wall content (C aw NO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in F E NO at 50 ml s -1 (F E NO 50 ), 4% in J aw NO, 16% in C aw NO, 8% in D aw NO and 12% in C A NO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

Clinical application of noninvasive diagnosis of liver fibrosis

OpenAIRE

ZHU Chuanlong

2015-01-01

Hepatic fibrosis is the common outcome of chronic liver diseases of various causes. At present, liver biopsy is the “gold standard” for the diagnosis of liver fibrosis, but it has limitations and is invasive, which leads to the development of noninvasive assessment of liver fibrosis. The article mainly introduces the technology and application of noninvasive diagnosis of liver fibrosis from the aspects of clinical manifestation, serology, and radiology. It has pointed out the clinical value o...

The Association between Plasma 25-Hydroxyvitamin D and Subgroups in Age-Related Macular Degeneration

DEFF Research Database (Denmark)

Singh, Amardeep; Falk, Mads Krüger; Subhi, Yousif

2013-01-01

To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis.......To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis....

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

Science.gov (United States)

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

2017-12-01

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

Mean Platelet Volume, Red Cell Distribution Width to Platelet Count Ratio, Globulin Platelet Index, and 16 Other Indirect Noninvasive Fibrosis Scores: How Much Do Routine Blood Tests Tell About Liver Fibrosis in Chronic Hepatitis C?

Science.gov (United States)

Thandassery, Ragesh B; Al Kaabi, Saad; Soofi, Madiha E; Mohiuddin, Syed A; John, Anil K; Al Mohannadi, Muneera; Al Ejji, Khalid; Yakoob, Rafie; Derbala, Moutaz F; Wani, Hamidullah; Sharma, Manik; Al Dweik, Nazeeh; Butt, Mohammed T; Kamel, Yasser M; Sultan, Khaleel; Pasic, Fuad; Singh, Rajvir

2016-07-01

Many indirect noninvasive scores to predict liver fibrosis are calculated from routine blood investigations. Only limited studies have compared their efficacy head to head. We aimed to compare these scores with liver biopsy fibrosis stages in patients with chronic hepatitis C. From blood investigations of 1602 patients with chronic hepatitis C who underwent a liver biopsy before initiation of antiviral treatment, 19 simple noninvasive scores were calculated. The area under the receiver operating characteristic curves and diagnostic accuracy of each of these scores were calculated (with reference to the Scheuer staging) and compared. The mean age of the patients was 41.8±9.6 years (1365 men). The most common genotype was genotype 4 (65.6%). Significant fibrosis, advanced fibrosis, and cirrhosis were seen in 65.1%, 25.6, and 6.6% of patients, respectively. All the scores except the aspartate transaminase (AST) alanine transaminase ratio, Pohl score, mean platelet volume, fibro-alpha, and red cell distribution width to platelet count ratio index showed high predictive accuracy for the stages of fibrosis. King's score (cutoff, 17.5) showed the highest predictive accuracy for significant and advanced fibrosis. King's score, Göteborg university cirrhosis index, APRI (the AST/platelet count ratio index), and Fibrosis-4 (FIB-4) had the highest predictive accuracy for cirrhosis, with the APRI (cutoff, 2) and FIB-4 (cutoff, 3.25) showing the highest diagnostic accuracy.We derived the study score 8.5 - 0.2(albumin, g/dL) +0.01(AST, IU/L) -0.02(platelet count, 10/L), which at a cutoff of >4.7 had a predictive accuracy of 0.868 (95% confidence interval, 0.833-0.904) for cirrhosis. King's score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-01-15

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Validation of Shear Wave Elastography Cutoff Values on the Supersonic Aixplorer for Practical Clinical Use in Liver Fibrosis Staging.

Science.gov (United States)

Dhyani, Manish; Grajo, Joseph R; Bhan, Atul K; Corey, Kathleen; Chung, Raymond; Samir, Anthony E

2017-06-01

The purpose of this study was to determine the validity of previously established ultrasound shear wave elastography (SWE) cut-off values (≥F2 fibrosis) on an independent cohort of patients with chronic liver disease. In this cross-sectional study, approved by the institutional review board and compliant with the Health Insurance Portability and Accountability Act, 338 patients undergoing liver biopsy underwent SWE using an Aixplorer ultrasound machine (SuperSonic Imagine, Aix-en-Provence, France). Median SWE values were calculated from sets of 10 elastograms. A single blinded pathologist evaluated METAVIR fibrosis staging as the gold standard. The study analyzed 277 patients with a mean age of 48 y. On pathologic examination, 212 patients (76.5%) had F0-F1 fibrosis, whereas 65 (23.5%) had ≥F2 fibrosis. Spearman's correlation of fibrosis with SWE was 0.456 (p Aixplorer SWE system. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Prognostic durability of liver fibrosis tests and improvement in predictive performance for mortality by combining tests.

Science.gov (United States)

Bertrais, Sandrine; Boursier, Jérôme; Ducancelle, Alexandra; Oberti, Frédéric; Fouchard-Hubert, Isabelle; Moal, Valérie; Calès, Paul

2017-06-01

There is currently no recommended time interval between noninvasive fibrosis measurements for monitoring chronic liver diseases. We determined how long a single liver fibrosis evaluation may accurately predict mortality, and assessed whether combining tests improves prognostic performance. We included 1559 patients with chronic liver disease and available baseline liver stiffness measurement (LSM) by Fibroscan, aspartate aminotransferase to platelet ratio index (APRI), FIB-4, Hepascore, and FibroMeter V2G . Median follow-up was 2.8 years during which 262 (16.8%) patients died, with 115 liver-related deaths. All fibrosis tests were able to predict mortality, although APRI (and FIB-4 for liver-related mortality) showed lower overall discriminative ability than the other tests (differences in Harrell's C-index: P fibrosis, 1 year in patients with significant fibrosis, and liver disease (MELD) score testing sets. In the training set, blood tests and LSM were independent predictors of all-cause mortality. The best-fit multivariate model included age, sex, LSM, and FibroMeter V2G with C-index = 0.834 (95% confidence interval, 0.803-0.862). The prognostic model for liver-related mortality included the same covariates with C-index = 0.868 (0.831-0.902). In the testing set, the multivariate models had higher prognostic accuracy than FibroMeter V2G or LSM alone for all-cause mortality and FibroMeter V2G alone for liver-related mortality. The prognostic durability of a single baseline fibrosis evaluation depends on the liver fibrosis level. Combining LSM with a blood fibrosis test improves mortality risk assessment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

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

Science.gov (United States)

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

2018-01-01

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

Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

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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.

An activated immune and inflammatory response targets the pancreas of newborn pigs with cystic fibrosis

Czech Academy of Sciences Publication Activity Database

Abu-El-Haija, M.; Šinkora, Marek; Meyerholz, D. K.; Welsh, M. J.; McCray, P.B.; Butler, J. E.; Uc, A.

2011-01-01

Roč. 11, č. 5 (2011), s. 506-515 ISSN 1424-3903 R&D Projects: GA MŠk ME09089 Institutional research plan: CEZ:AV0Z50200510 Keywords : cystic fibrosis * pancreatitis * flow cytometry Subject RIV: EC - Immunology Impact factor: 1.987, year: 2011

Morphometric alterations, steatosis, fibrosis and active caspase-3 detection in carbamate bendiocarb treated rabbit liver

Czech Academy of Sciences Publication Activity Database

Petrovová, E.; Purzyc, H.; Mazenský, D.; Luptáková, L.; Torma, N.; Sopoliga, I.; Sedmera, David

2015-01-01

Roč. 30, č. 2 (2015), s. 212-222 ISSN 1520-4081 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : bendiocarb * caspase-3 activity * fibrosis * toxicity * rabbit * liver Subject RIV: EA - Cell Biology Impact factor: 2.868, year: 2015

Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study.

Science.gov (United States)

Han, MeiLan K; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Noth, Imre; Lama, Vibha N; Moore, Bethany B; White, Eric S; Flaherty, Kevin R; Huffnagle, Gary B; Martinez, Fernando J

2014-07-01

The role of the lung microbiome in the pathogenesis of idiopathic pulmonary fibrosis is unknown. We investigated whether unique microbial signatures were associated with progression of idiopathic pulmonary fibrosis. Patients (aged 35-80 years) with idiopathic pulmonary fibrosis within 4 years of diagnosis from the Correlating Outcomes with biochemical Markers to Estimate Time-progression (COMET) in idiopathic pulmonary fibrosis study were followed up for a maximum of 80 weeks. Progression-free survival was defined as time to death, acute exacerbation, lung transplant, or decrease in forced vital capacity (FVC) of 10% or greater or decrease in diffusion capacity of the lung (DLCO) of 15% or greater. DNA was isolated from 55 samples of bronchoscopic alveolar lavage. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) to bacteria based on a 3% sequence divergence. Adjusted Cox models were used to identify OTUs that were significantly associated with progression-free survival at a pidiopathic pulmonary fibrosis is associated with the presence of specific members within the Staphylococcus and Streptococcus genera. Additional research will be needed to identify the specific bacterial species and to ascertain whether this is a causal association. National Institutes of Health. Copyright © 2014 Elsevier Ltd. All rights reserved.

T1 mapping for detection of left ventricular myocardial fibrosis in hypertrophic cardiomyopathy: A preliminary study

International Nuclear Information System (INIS)

Lu, Minjie; Zhao, Shihua; Yin, Gang; Jiang, Shiliang; Zhao, Tao; Chen, Xiuyu; Tian, Liangxin; Zhang, Yan; Wei, Yunqing; Liu, Qiong; He, Zuoxiang; Xue, Hui; An, Jing; Shah, Saurabh

2013-01-01

Purpose: To investigate the diagnostic value of T1 mapping imaging of evaluating fibrosis in patients with hypertrophic cardiomyopathy (HCM). Materials and methods: 21 subjects with HCM and 18 healthy volunteers underwent conventional late gadolinium enhancement (LGE) imaging and T1 mapping imaging. The region of myocardium in HCM is divided into remote area of LGE, peri-LGE, LGE (halo-like LGE and typical patchy LGE). These regions combined with normal volunteers’ myocardium were calculated by the reduced percent of T1 value (RPTV). Results: The RPTV in healthy volunteers was no significant comparing with that in the remote area of LGE in HCM subjects (3.98 ± 3.19 vs. 3.34 ± 2.75, P > 0.05). There were significant statistical differences in pairwise among the remote area of LGE, peri-LGE, halo-like LGE and typical patchy LGE in the RPTV (P < 0.0001). ROC curves indicated that the T1 mapping imaging has a greater area under the curve comparing with that of traditional LGE imaging (0.975 ± 0.07 vs. 0.753 ± 0.26, P < 0.0001). Conclusions: HCM has a high prevalence of fibrosis and with varying severity. T1 mapping imaging can be a useful method to evaluate the severity of the fibrosis in HCM

Transient elastography for liver fibrosis diagnosis

DEFF Research Database (Denmark)

Andersen, Ellen Sloth; Christensen, Peer Brehm; Weis, Nina

2008-01-01

Liver biopsy is considered the "golden standard" for assessment of hepatic fibrosis. However, the procedure has limitations because of inconvenience and rare but serious complications as bleeding. Furthermore, sampling errors are frequent, and interobserver variability often poses problems....... Recently, a modified ultrasound scanner (transient elastography) has been developed to assess fibrosis. The device measures liver elasticity, which correlates well with the degree of fibrosis. Studies have shown that transient elastography is more accurate in diagnosing cirrhosis than minor to moderate...... to be a valuable diagnostic procedure and follow-up of patients with chronic liver diseases....

Transient elastography for liver fibrosis diagnosis

DEFF Research Database (Denmark)

Andersen, Ellen Sloth; Christensen, Peer Brehm; Weis, Nina

2009-01-01

Liver biopsy is considered the "golden standard" for assessment of hepatic fibrosis. However, the procedure has limitations because of inconvenience and rare but serious complications as bleeding. Furthermore, sampling errors are frequent, and interobserver variability often poses problems....... Recently, a modified ultrasound scanner (transient elastography) has been developed to assess fibrosis. The device measures liver elasticity, which correlates well with the degree of fibrosis. Studies have shown that transient elastography is more accurate in diagnosing cirrhosis than minor to moderate...... to be a valuable diagnostic procedure and follow-up of patients with chronic liver diseases....

[Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease].

Science.gov (United States)

Kim, Sun Min; Sohn, Joo Hyun; Kim, Tae Yeob; Roh, Young Wook; Eun, Chang Soo; Jeon, Yong Cheol; Han, Dong Soo; Oh, Young Ha

2009-12-01

The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3). All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

Emotional Intelligence Mediates the Relationship between Age and Subjective Well-Being.

Science.gov (United States)

Chen, Yiwei; Peng, Yisheng; Fang, Ping

2016-07-01

Individuals' Subjective Well-being (SWB) increases as they grow older. Past literature suggests that emotional intelligence may increase with age and lead to higher levels of SWB in older adults. The primary purpose of the present study was to test whether emotional intelligence would mediate the relationship between age and SWB. A total of 360 Chinese adults (age range: 20 to 79 years old) participated in this study. They filled out questionnaires that assessed their age, life satisfaction (The Satisfaction with Life Scale), affective well-being (The Positive and Negative Affect Schedule), and emotional intelligence (The Wong and Law Emotional Intelligence Scale). Using Structural Equation Modeling, the mediation model was supported, χ(2) (75) = 194.21, p Emotional intelligence partially mediated the relationship between age and life satisfaction, and fully mediated the relationship between age and affective well-being. The findings suggest that older adults may use their increased emotional intelligence to enhance their SWB. © The Author(s) 2016.

CFTR Genotype and Maximal Exercise Capacity in Cystic Fibrosis: A Cross-sectional Study.

Science.gov (United States)

Radtke, Thomas; Hebestreit, Helge; Gallati, Sabina; Schneiderman, Jane E; Braun, Julia; Stevens, Daniel; Hulzebos, Erik Hj; Takken, Tim; Boas, Steven R; Urquhart, Don S; Lands, Larry C; Tejero, Sergio; Sovtic, Aleksandar; Dwyer, Tiffany; Petrovic, Milos; Harris, Ryan A; Karila, Chantal; Savi, Daniela; Usemann, Jakob; Mei-Zahav, Meir; Hatziagorou, Elpis; Ratjen, Felix; Kriemler, Susi

2018-02-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with cystic fibrosis may be an important determinant of maximal exercise capacity in cystic fibrosis. Previous studies on the relationship between CFTR genotype and maximal exercise capacity are scarce and contradictory. This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (V.O2peak), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. In an international, multicenter, cross-sectional study, we collected data on CFTR genotype and cardiopulmonary exercise tests in patients with cystic fibrosis who were ages 8 years and older. CFTR mutations were classified into functional classes I–V. The final analysis included 726 patients (45% females; age range, 8–61 yr; forced expiratory volume in 1 s, 16 to 123% predicted) from 17 cystic fibrosis centers in North America, Europe, Australia, and Asia, all of whom had both valid maximal cardiopulmonary exercise tests and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (V.O2peak, 77.3 ± 19.1% predicted), but values were comparable among different CFTR classes. We did not detect an association between CFTR genotype functional classes I–III and either V.O2peak (percent predicted) (adjusted β = −0.95; 95% CI, −4.18 to 2.29; P = 0.57) or maximum work rate (Wattmax) (adjusted β = −1.38; 95% CI, −5.04 to 2.27; P = 0.46) compared with classes IV–V. Those with at least one copy of a F508del-CFTR mutation and one copy of a class V mutation had a significantly lower V.O2peak (β = −8.24%; 95% CI, −14.53 to −2.99; P = 0.003) and lower Wattmax (adjusted β = −7.59%; 95% CI, −14.21 to −0.95; P = 0.025) than those with two copies of a class II mutation. On the basis of linear regression analysis adjusted for

Pregnancy and cystic fibrosis: Approach to contemporary management

Science.gov (United States)

Tay, George; Callaway, Leonie; Bell, Scott C

2014-01-01

Over the previous 50 years survival of patients with cystic fibrosis has progressively increased. As a result of improvements in health care, increasing numbers of patients with cystic fibrosis are now considering starting families of their own. For the health care professionals who look after these patients, the assessment of the potential risks, and the process of guiding prospective parents through pregnancy and beyond can be both challenging and rewarding. To facilitate appropriate discussions about pregnancy, health care workers must have a detailed understanding of the various important issues that will ultimately need to be considered for any patient with cystic fibrosis considering parenthood. This review will address these issues. In particular, it will outline pregnancy outcomes for mothers with cystic fibrosis, issues that need to be taken into account when planning a pregnancy and the management of pregnancy for mothers with cystic fibrosis or mothers who have undergone organ transplantation as a result of cystic fibrosis. PMID:27512443

Performance of transient elastography and serum fibrosis biomarkers for non-invasive evaluation of recurrent fibrosis after liver transplantation: A meta-analysis.

Science.gov (United States)

Bhat, Mamatha; Tazari, Mahmood; Sebastiani, Giada

2017-01-01

Recurrent fibrosis after liver transplantation (LT) impacts on long-term graft and patient survival. We performed a meta-analysis to compare the accuracy of non-invasive methods to diagnose significant recurrent fibrosis (stage F2-F4) following LT. Studies comparing serum fibrosis biomarkers, namely AST-to-platelet ratio index (APRI), fibrosis score 4 (FIB-4), or transient elastography (TE) with liver biopsy in LT recipients were systematically identified through electronic databases. In the meta-analysis, we calculated the weighted pooled odds ratio and used a fixed effect model, as there was no significant heterogeneity between studies. Eight studies were included for APRI, four for FIB-4, and twelve for TE. The mean prevalence of significant liver fibrosis was 37.4%. The summary odds ratio was significantly higher for TE (21.17, 95% CI confidence interval 14.10-31.77, p = 1X10-30) as compared to APRI (9.02, 95% CI 5.79-14.07; p = 1X10-30) and FIB-4 (7.08, 95% CI 4.00-12.55; p = 1.93X10-11). In conclusion, TE performs best to diagnose recurrent fibrosis in LT recipients. APRI and FIB-4 can be used as an estimate of significant fibrosis at centres where TE is not available. Longitudinal assessment of fibrosis by means of these non-invasive tests may reduce the need for liver biopsy.

Lack of efficacy of Lactobacillus GG in reducing pulmonary exacerbations and hospital admissions in children with cystic fibrosis: A randomised placebo controlled trial.

Science.gov (United States)

Bruzzese, Eugenia; Raia, Valeria; Ruberto, Eliana; Scotto, Riccardo; Giannattasio, Antonietta; Bruzzese, Dario; Cavicchi, Maria Cristina; Francalanci, Michela; Colombo, Carla; Faelli, Nadia; Daccò, Valeria; Magazzù, Giuseppe; Costa, Stefano; Lucidi, Vincenzina; Majo, Fabio; Guarino, Alfredo

2017-11-08

Intestinal dysbiosis has been described in Cystic Fibrosis (CF) and probiotics have been proposed to restore microbial composition. Aim of the study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) on clinical outcomes in children with cystic fibrosis (CF). A multicentre, randomised double-blind, clinical trial was conducted in children with CF. After 6months of baseline assessment, enrolled children (2 to 16years of age) received Lactobacillus GG (6×10 9 CFU/day) or placebo for 12months. Primary outcomes were proportion of subjects with at least one pulmonary exacerbation and hospitalisation over 12months. Secondary endpoints were total number of exacerbations and hospitalisations, pulmonary function, and nutritional status. Ninety-five patients were enrolled (51/95 female; median age of 103±50months). In a multivariate GEE logistic analysis, the odds of experiencing at least one exacerbation was not significantly different between the two groups, also after adjusting for the presence of different microbial organisms and for the number of pulmonary exacerbations within 6months before randomisation (OR 0.83; 95% CI 0.38 to 1.82, p=0.643). Similarly, LGG supplementation did not significantly affect the odds of hospitalisations (OR 1.67; 95% CI 0.75 to 3.72, p=0.211). No significant difference was found for body mass index and FEV1. LGG supplementation had no effect on respiratory and nutritional outcomes in this large study population of children with CF under stringent randomised clinical trial conditions. Whether earlier interventions, larger doses, or different strains of probiotics may be effective is unknown. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Genetics Home Reference: idiopathic pulmonary fibrosis

Science.gov (United States)

... these health problems has idiopathic pulmonary fibrosis . Other respiratory diseases, some of which are less serious, can cause similar signs and symptoms. In people with idiopathic pulmonary fibrosis , scarring of the lungs increases over time until the lungs can no longer ...

Revisiting the Structure of Subjective Well-Being in Middle-Aged Adults

Science.gov (United States)

Chmiel, Magda; Brunner, Martin; Martin, Romain; Schalke, Daniela

2012-01-01

Subjective well-being is a broad, multifaceted construct comprising general satisfaction with life, satisfaction with life domains (health, family, people, free time, self, housing, work, and finances), positive affect, and negative affect. Drawing on representative data from middle-aged adults (N = 738), the authors used three different…

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

Directory of Open Access Journals (Sweden)

Félix O. Dickinson

2005-06-01

��William Soler” Pediatric Hospital between 1988 and 2002, were described. Percentages were calculated according to age groups, sex, most frequent symptoms and signs, reason for admission, length of stay, antibiotics administered and others. Results: No deaths were reported during the studied period, it was observed a predominance of pediatric ages (86.6 %, males (67 % and white-colored skin patients (80 %. The commonest symptoms were respiratory infections (67 %, low birth weight (48 % and digestive disorders (25 %, which began as an average at 20.6 months of age. The genetic characterization was mostly delta F 508 (66 %. One of the main causes of admission was to receive antibiotic therapy (45 % for treating lower respiratory infections (22 % and cystic fibrosis (15 %. There was a total of 72 admissions and 1 088 days of hospital stay were accumulated, with an average of 15 days. In nearly all the cases, antibiotic therapy was applied due to the isolates of Psedomona aeruginosa as a cause of respiratory infection.11 different antibiotics were used, of which the most frequent were amikacin, ceftazidime, gentamicin, trobamicin and cyproflaxacin. The most common combination was that of a beta-lactamic and an aminoglucoside.

Clinical significance of changes of serum osteocalcin (BGP) levels in subjects of different age-groups

International Nuclear Information System (INIS)

Jiang Lihua; Zhang Jin; Han Cuihua; Ouyang Qiaohong

2006-01-01

Objective: To investigate the changes of serum BGP levels in different age-groups. Methods: Serum BGP levels were determined with RIA in 306 subjects of different age-groups. Results: The serum BGP levels were highest in subjects of the pre-adolescent group (age5-15, n=60, vs other groups, all P 50, n=80, P<0.001). Levels in the middle age group were the lowest and were significantly lower than those in the old age group (P<0.001). No sex related differences were observed in the pre-adolescent and middle age groups, but in the youth group, serum BGP levels were significantly higher in the males than those in the females (P<0.05). However, in the old age group, the reverse was true i.e. values being significantly higher in the females (vs males, P<0.01). Conclusion: Serum BGP levels varied greatly among the different age groups. (authors)

Indapamide-induced prevention of myocardial fibrosis in spontaneous hypertension rats is not nitric oxide-related

Czech Academy of Sciences Publication Activity Database

Janega, P.; Kojšová, S.; Jendeková, L.; Babál, P.; Pecháňová, Olga

2007-01-01

Roč. 56, č. 6 (2007), s. 825-828 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : indapamide * myocardial fibrosis * genetic hypertension Subject RIV: ED - Physiology Impact factor: 1.505, year: 2007

Context Influences on the Subjective Experience of Aging: The Impact of Culture and Domains of Functioning.

Science.gov (United States)

O'Brien, Erica L; Hess, Thomas M; Kornadt, Anna E; Rothermund, Klaus; Fung, Helene; Voss, Peggy

2017-08-01

Attitudes about aging influence how people feel about their aging and affect psychological and health outcomes in later life. Given cross-cultural variability in such attitudes, the subjective experience of aging (e.g., subjective age [SA]) may also vary, potentially accounting for culture-specific patterns of aging-related outcomes. Our study explored cultural variation in SA and its determinants. American (N = 569), Chinese (N = 492), and German (N = 827) adults aged 30-95 years completed a questionnaire that included instruments measuring basic demographic information, SA, beliefs about thresholds of old age, control over life changes, and age dependency of changes in eight different life domains (i.e., family, work). Analyses revealed consistency across cultures in the domain-specificity of SA, but differences in the amount of shared variance across domains (e.g., Chinese adults exhibited greater homogeneity across domains than did Americans and Germans). Cultural differences were also observed in levels of SA in some domains, which were attenuated by domain-specific beliefs (e.g., control). Interestingly, beliefs about aging accounted for more cultural variation in SA than did sociodemographic factors (e.g., education). Our results demonstrate that subjective perceptions of aging and everyday functioning may be best understood from a perspective focused on context (i.e., culture, life domain). Given its important relation to functioning, examination of cross-cultural differences in the subjective experience of aging may highlight factors that determine variations in aging-related outcomes that then could serve as targets of culture-specific interventions promoting well-being in later life. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Element analysis of teeth from children with and without cystic fibrosis by PIXE-PIGE

International Nuclear Information System (INIS)

Cua, F.T.

1990-01-01

The objective of this research is to determine whether there is a difference in the Ca, P, Fe, F, Mg, and Sr concentrations in teeth from children with and without cystic fibrosis (CF) as a function of age, sex of the child, maternal smoking habit, maternal drinking habit, and fluoridation of water supply. The nuclear analytical methods used were Proton-Induced X-Ray Emission (PIXE) and Proton-Induced Gamma Emission (PIGE). The findings are: (1) the concentration of Mg is higher in the teeth of children with cystic fibrosis who took antibiotics other than tetracycline (CF+NT) than in non-cystic fibrosis (NCF) teeth for the 'female' category; (2) P concentration is less in (CF+NT) teeth for the 'age greater than ten' group; (3) Fe concentration is greater for females in the NCF group; (4) Ca and Fe concentrations are lower for CF than for NCF in the 'mother smokes' group; (5) F and Sr concentrations for CF+NT are higher for the 'mother drinks' group than for the 'mother does not drink' group; (6) 'mother smokes' shows a depletion of Ca and Fe compared to 'mother does not smoke' for CF+NT. (7) 'fluoridation of water supply' shows an increase in F, except for NCF teeth. (author)

Laparoscopic cholecystectomy in adult cystic fibrosis.

LENUS (Irish Health Repository)

McGrath, D S

2012-02-03

Two female patients with Cystic Fibrosis, attending the Adult Regional Cystic Fibrosis centre at the Cork University Hospital, were investigated for upper abdominal pain and found to have gallstones at ultrasonography. Laparoscopic cholecystectomy was performed successfully and, without complication, in both patients.

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

Directory of Open Access Journals (Sweden)

Kalinca da Silva OLIVEIRA

2015-03-01

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

False Memories in Children and Adults: Age, Distinctiveness, and Subjective Experience.

Science.gov (United States)

Ghetti, Simona; Qin, Jianjian; Goodman, Gail S.

2002-01-01

Investigated developmental trends associated with the Deese/Roediger-McDermott false-memory effect, the role of distinctive information, and subjective experience of true/false memories. Found that 5-year-olds recalled more false memories than adults but no age differences in recognition of critical lures. Distinctive information reduced false…

Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C

OpenAIRE

Stauber, Rudolf E; Lackner, Carolin

2007-01-01

Assessment of hepatic fibrosis is important for determining prognosis, guiding management decisions, and monitoring disease. Histological evaluation of liver biopsy specimens is currently considered the reference test for staging hepatic fibrosis. Since liver biopsy carries a small but significant risk, noninvasive tests to assess hepatic fibrosis are desirable. This editorial gives an overview on noninvasive methods currently available to determine hepatic fibrosis and their diagnostic accur...

Ultrasonic nonlinearity of AISI316 austenitic steel subjected to long-term isothermal aging

Energy Technology Data Exchange (ETDEWEB)

Gong, Won Sik; Kim, Chung Seok [Dept. of Materials Science and Engineering, Chosun University, Gwangju (Korea, Republic of)

2014-06-15

This study presents the ultrasonic nonlinearity of AISI316 austenitic stainless steels subjected to longterm isothermal aging. These steels are attractive materials for use in industrial mechanical structures because of their strength at high-temperatures and their chemical stability. The test materials were subjected to accelerated heat-treatment in an electrical furnace for a predetermined aging duration. The variations in the ultrasonic nonlinearity and microstructural damage were carefully evaluated through observation of the microstructure. The ultrasonic nonlinearity stiffly dropped after aging for up to 1000 h and, then, monotonously decreased. The polygonal shape of the initial grain structures changed to circular, especially as the annealing twins in the grains dissolved and disappeared. The delta ferrite on the grain boundaries could not be observed at 1000 h of aging, and these continuously transformed into their sigma phases. Consequently, in the intial aging period, the rapid decrease in the ultrasonic nonlinearity was caused by voids, dislocations, and twin annihilation. The continuous monotonic decrease in the ultrasonic nonlinearity after the first drop resulted from the generation of Cr{sub 23}C{sub 6} precipitates and σ phases.

Metabolic and Cardiovascular Ageing Indices in Relation to Glycated Haemoglobin in Healthy and Diabetic Subjects.

Science.gov (United States)

Suvarna H I, Shruthi; Moodithaya, Shailaja; Sharma, Raghava

2017-01-01

Ageing is a natural phenomenon that has tremendous amount of control over normal physiological functions. Diabetes mellitus and ageing share common symptoms like stiffness and loss of functioning of tissues due to cross-liked proteins and free radicals. Glycated Haemoglobin (HbA1c) is often used as a stable cumulative index of glycemic control and has shown that even in non-diabetic adults, there is a steady increase in HbA1c levels with age. Aim of the study is to evaluate the strength of association of HbA1c with metabolic and cardiovascular ageing indices in subjects between the age group of 40 to 60 yrs. A total of 220 subjects, with (n=110) and without (n=110) diabetes were assessed for the metabolic and cardiovascular ageing indices. BMI, waist hip ratio, fat percentage, Fasting blood sugar and HbA1c were assessed as metabolic ageing indices. The cardiovascular ageing indices measured were resting heart rate, blood pressure and heart rate variability. Ageing indices were compared between subjects with and without diabetes using independent' t' test and showed that the T2DM group exhibit significant accelerated ageing as compared to that of the controls. Pearson's and partial correlation coefficient was used to assess the association of HbA1c with the ageing indices without and with controlling for chronological age, indicated that, strength of association of levels of HBA1c with cardiovascular and other metabolic indices of ageing is statistically significant. The study concludes that the tightness of glycemic control has a significant impact on the biological ageing process. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Subjective insomnia is associated with low sleep efficiency and fatigue in middle-aged women.

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Hirose, A; Terauchi, M; Akiyoshi, M; Owa, Y; Kato, K; Kubota, T

2016-08-01

Many middle-aged women are affected by sleep disturbance. We investigated how subjective insomnia is associated with objective sleep parameters and other background characteristics. This cross-sectional study used baseline data obtained from 95 women aged 40-59 years who participated in another study assessing the effects of a dietary supplement. Participants wore an actigraph unit for 3 days to collect information concerning physical activities and objective sleep parameters and were then evaluated for body composition, cardiovascular parameters, and menopausal symptoms including insomnia and fatigue, and lifestyle factors. Stratifying Athens Insomnia Scale scores as low (0-5 points, control group) and high (≥ 6 points, subjective insomnia group), we sought to identify the parameters that are independently associated with subjective insomnia. Women with subjective insomnia (n = 30) had lower sleep efficiency than did the controls. They were also older; had more live births, lower height, higher body mass index, lower ankle brachial index, and more severe menopausal symptoms including fatigue; took more naps; smoked more cigarettes; and more of them were full-time workers. Multivariate logistic regression analysis revealed that low sleep efficiency (adjusted odds ratio, 1.44 per 1% decrease in sleep efficiency; 95% confidence interval 1.06-2.05) and fatigue assessed with Brief Fatigue Inventory (BFI) (adjusted odds ratio, 1.57 per 1-point increase in BFI score; 95% confidence interval 1.19-2.13) were independent contributors to subjective insomnia. Low sleep efficiency and feeling of fatigue were found to be independently associated with subjective insomnia in middle-aged women.

TGF-β/Smad signaling in renal fibrosis

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Xiao-Ming eMeng

2015-03-01

Full Text Available TGF-β (transforming growth factor-β is well identified as a central mediator in renal fibrosis. TGF-β initiates canonical and non-canonical pathways to exert multiple biological effects. Among them, Smad signaling is recognized as a major pathway of TGF- signaling in progressive renal fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases-dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7 leads to accumulation and activation of myofibroblasts, overproduction of ECM (extracellular matrix, and reduction in ECM degradation in the diseased kidney. Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for renal fibrosis in various models of kidney diseases. In contrast, another downstream effecter of TGF-β/Smad signaling pathway, Smad2, exerts its renal protective role by counter-regulating the Smad3. Furthermore, recent studies demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR-200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR-200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3-mediated renal fibrosis in various mouse models of chronic kidney diseases. Taken together, TGF-/Smad signaling plays an important role in renal fibrosis. Targeting TGF-β/Smad3 signaling may represent a specific and effective therapy for chronic kidney diseases associated with renal fibrosis.

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

DEFF Research Database (Denmark)

Bracht, Thilo; Mölleken, Christian; Ahrens, Maike

2016-01-01

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

Congenital hepatic fibrosis associated with von Recklinghausen's disease Fibrosis hepática congénita asociada a enfermedad de von Recklinghausen

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O. A. Jorge

2006-09-01

Full Text Available Congenital hepatic fibrosis is characterized by a ductal plate malformation with duct-like structures and fibrosis. It manifests clinically with portal hypertension and may be associated with multiple congenital defects. We present the case of a 16-year-old male with splenomegaly, leukopenia and thrombocytopenia, esophageal varices, and a histopathological diagnosis of congenital hepatic fibrosis. He exhibits "café au lait' spots and "Lisch' nodules, with a diagnosis of von Recklinghausen's disease. Congenital hepatic fibrosis belongs to the so-called fibropolycystic diseases, in which there is a disordered interaction between cells and the extracellular matrix. Von Recklinghausen's disease affects tissues derived from the neural crest and its diagnosis is based on clinical criteria. It is associated with multiple diseases. We describe its association with congenital hepatic fibrosis for the first time.La fibrosis hepática congénita se origina como consecuencia de una malformación de la placa ductal con estructuras tipo ductales acompañadas de fibrosis. Se manifiesta con hipertensión portal y puede asociarse a múltiples defectos congénitos. Presentamos un varón de 16 años con esplenomegalia, leuco- y plaquetopenia, varices esofágicas y diagnóstico histopatológico de fibrosis hepática congénita. La exploración física mostraba la existencia de manchas de "café con leche' y nódulos de "Lisch' con diagnóstico de enfermedad de von Recklinghausen. La fibrosis hepática congénita forma parte de las enfermedades fibropoliquísticas donde existiría una alteración en la interacción entre las células y la matriz extracelular. La enfermedad de von Recklinghausen afecta a los tejidos derivados de la cresta neural y su diagnóstico se basa en criterios clínicos. Se asocia a múltiples patologías. Presentamos por primera vez su asociación con fibrosis hepática congénita.

Epithelial NEMO/IKKγ limits fibrosis and promotes regeneration during pancreatitis.

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Chan, Lap Kwan; Gerstenlauer, Melanie; Konukiewitz, Björn; Steiger, Katja; Weichert, Wilko; Wirth, Thomas; Maier, Harald Jakob

2017-11-01

Inhibitory κB kinase (IKK)/nuclear factor κB (NF-κB) signalling has been implicated in the pathogenesis of pancreatitis, but its precise function has remained controversial. Here, we analyse the contribution of IKK/NF-κB signalling in epithelial cells to the pathogenesis of pancreatitis by targeting the IKK subunit NF-κB essential modulator (NEMO) (IKKγ), which is essential for canonical NF-κB activation. Mice with a targeted deletion of NEMO in the pancreas were subjected to caerulein pancreatitis. Pancreata were examined at several time points and analysed for inflammation, fibrosis, cell death, cell proliferation, as well as cellular differentiation. Human samples were used to corroborate findings established in mice. In acute pancreatitis, NEMO deletion in the pancreatic parenchyma resulted in minor changes during the early phase but led to the persistence of inflammatory and fibrotic foci in the recovery phase. In chronic pancreatitis, NEMO deletion aggravated inflammation and fibrosis, inhibited compensatory acinar cell proliferation, and enhanced acinar atrophy and acinar-ductal metaplasia. Gene expression analysis revealed sustained activation of profibrogenic genes and the CXCL12/CXCR4 axis in the absence of epithelial NEMO. In human chronic pancreatitis samples, the CXCL12/CXCR4 axis was activated as well, with CXCR4 expression correlating with the degree of fibrosis. The aggravating effects of NEMO deletion were attenuated by the administration of the CXCR4 antagonist AMD3100. Our results suggest that NEMO in epithelial cells exerts a protective effect during pancreatitis by limiting inflammation and fibrosis and improving acinar cell regeneration. The CXCL12/CXCR4 axis is an important mediator of that effect and may also be of importance in human chronic pancreatitis. 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/.

Psychosocial problems in children with cystic fibrosis

DEFF Research Database (Denmark)

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

2007-01-01

AIM: To compare the well-being of children (7-14 years) with cystic fibrosis (CF) (n = 43) with the well-being of healthy controls (n = 1121). METHODS: The self-report questionnaire Beck Youth Inventories (BYI) was used to study depression, anxiety, anger, disruptive behaviour and self-concept in......AIM: To compare the well-being of children (7-14 years) with cystic fibrosis (CF) (n = 43) with the well-being of healthy controls (n = 1121). METHODS: The self-report questionnaire Beck Youth Inventories (BYI) was used to study depression, anxiety, anger, disruptive behaviour and self......-concept in children with CF. A measure of social desirability was included as well as body mass index (BMI) and percentage of predicted forced expiratory volume in one second (FEV(1)) as measures of health status. RESULTS: The children with CF did not differ from the norm group concerning depression, disruptive...... behaviour and self-concept. Young children with CF (7-10 years) and boys with CF scored significantly higher on anxiety. Girls with CF scored significantly lower on anger than controls. BMI was not associated with any of the BYI subscales. In patients aged 11-14 years, there was a significant correlation...

Life Satisfaction, Self-Esteem, and Subjective Age in Women across the Life Span

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Borzumato-Gainey, Christine; Kennedy, Alison; McCabe, Beth; Degges-White, Suzanne

2009-01-01

A study of 320 women, ages 21 to 69, explored the relations among relationship status, subjective age, self-esteem, and life satisfaction. Women in married or partnered relationships had higher levels of life satisfaction than did single women. Women in their 30s and 40s had significantly lower levels of life satisfaction than did other age…

[State of accommodation depending on age of emmetropic and hypermetropic subjects engaged in diamond sorting].

Science.gov (United States)

Feĭgin, A A; Korniushina, T A

1995-01-01

Accommodation was studied in 449 diamond sorters aged 17 to 51 engaged in this work for 1 to 34 years with emmetropic and hypermetropic refraction. Questionnaires helped detect subjects who had no complaints of vision (group A) and those with asthenopia complaints (group B). In both groups, in emmetropic and hypermetropic subjects, the furthest point of clear vision was converging the eye by 1.96 +/- 0.04 diopters on an average, that is, there was pseudomyopia. In hypermetropic subjects with occupational ophthalmopathy the nearest point is withdrawn starting from the age of 31-35 till it merges with the furthest point in subjects over 45, that is, the accommodation volume becomes nearly nuel. The results of this study contradict the assumption existing in ophthalmology about an earlier onset of presbyopia in hypermetropia than in other types of refraction. Early correction of near vision is connected with superimposition of accommodation deterioration in ametropia. It is recommended to carry out rehabilitative measure as soon as the first asthenopia signs manifest; these measures should be aimed at weakening of refraction by the site of the furthest clear vision point. In subjects aged 31-35 with occupational ophthalmopathy refraction by the nearest clear vision point should be enhanced if possible.

Growth retardation and reduced growth hormone secretion in cystic fibrosis. Clinical observations from three CF centers.

Science.gov (United States)

Ciro, D'Orazio; Padoan, Rita; Blau, Hannah; Marostica, Anna; Fuoti, Maurizio; Volpi, Sonia; Pilotta, Alba; Meyerovitch, Joseph; Sher, Daniel; Assael, Baroukh M

2013-03-01

Growth delay in cystic fibrosis is frequent and is usually the result of several interacting causes. It most often derives from severe respiratory impairment and severe malabsorption. There are however patients whose clinical condition is not severe enough to be held accountable for this phenomenon. We aimed at describing patients who showed growth delay, who were not affected by severe pulmonary disease or malabsorption and who, when tested, showed a reduced GH secretion after stimulation with conventional agents. We noticed a disproportionately large prevalence of growth hormone (GH) release deficit (GHRD) in pediatric cystic fibrosis (CF) patients. We examined all patients under our care in the period 2006-11, who were older than 5 and younger than 16 years old. We focussed on those who fell below the 3rd height percentile, or whose growth during the previous 18 months faltered by >2SD, and who did not present clinical conditions that could reasonably explain their failure to thrive. These patients were subjected to standard GH provocative tests. Out of 285 who matched the age criterion, 33 patients also matched the height percentile criterion. While 15/33 suffered clinical conditions that could reasonably explain their failure to thrive, 18/33 underwent GH release provocative tests and 12/18 showed a release deficit. We conclude that impaired GH secretion is more frequent among CF patients compared to the prevalence of GH deficiency in the general population and that GH release impairment may be an independent cause of growth delay in CF. Our findings are in agreement with recent studies that have described low GH levels in CF piglets and in neonates with CF [1]. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

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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.

Combined Pulmonary Fibrosis and Emphysema Syndrome

Science.gov (United States)

Rounds, Sharon I. S.

2012-01-01

There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs.

Science.gov (United States)

Ford, Jordan; McEndaffer, Laura; Renshaw, Randall; Molesan, Alex; Kelly, Kathleen

2017-11-01

Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%-45%) and 2 of 41 controls (5%; 95% CI, 0.1%-16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions ( P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.

Routine Laboratory Blood Tests May Diagnose Significant Fibrosis in Liver Transplant Recipients with Chronic Hepatitis C: A 10 Year Experience.

Science.gov (United States)

Sheen, Victoria; Nguyen, Heajung; Jimenez, Melissa; Agopian, Vatche; Vangala, Sitaram; Elashoff, David; Saab, Sammy

2016-03-28

The aims of our study were to determine whether routine blood tests, the aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) and Fibrosis 4 (Fib-4) scores, were associated with advanced fibrosis and to create a novel model in liver transplant recipients with chronic hepatitis C virus (HCV). We performed a cross sectional study of patients at The University of California at Los Angeles (UCLA) Medical Center who underwent liver transplantation for HCV. We used linear mixed effects models to analyze association between fibrosis severity and individual biochemical markers and mixed effects logistic regression to construct diagnostic models for advanced fibrosis (METAVIR F3-4). Cross-validation was used to estimate a receiving operator characteristic (ROC) curve for the prediction models and to estimate the area under the curve (AUC). The mean (± standard deviation [SD]) age of our cohort was 55 (±7.7) years, and almost three quarter were male. The mean (±SD) time from transplant to liver biopsy was 19.9 (±17.1) months. The mean (±SD) APRI and Fib-4 scores were 3 (±12) and 7 (±14), respectively. Increased fibrosis was associated with lower platelet count and alanine aminotransferase (ALT) values and higher total bilirubin and Fib-4 scores. We developed a model that takes into account age, gender, platelet count, ALT, and total bilirubin, and this model outperformed APRI and Fib-4 with an AUC of 0.68 (p fibrosis more reliably than APRI and Fib-4 scores. This noninvasive calculation may be used clinically to identify liver transplant recipients with HCV with significant liver damage.

Age-related changes in brain perfusion of normal subjects detected by 99mTc-HMPAO SPECT

International Nuclear Information System (INIS)

Krausz, Y.; Karger, H.; Chisin, R.; Bonne, O.; Gorfine, M.; Lerer, B.

1998-01-01

Previous functional imaging data generally show impairment in global cerebral blood flow (CBF) with age. Conflicting data, however, concerning age-related changes in regional CBF (rCBF) have been reported. We examined the relative rCBF in a sample of healthy subjects of various ages, to define and localize any age-related CBF reduction. Twenty-seven healthy subjects (17 male, 10 female; mean age 49 ± 15, range 26-71, median 47 years) were studied by 99m Tc-HMPAO brain SPECT. The younger age group consisted of subjects below, the older group above 47 years of age, respectively. Analysis was performed by applying three preformed templates, each containing delineated regions of interest (ROIs), to three transaxial brain slices at approximately 4, 6, and 7 cm above the orbitomeatal line (OML). The average number of counts for each ROI was normalized to mean uptake of the cerebellum and of the whole brain slice. Globally, 99m Tc-HMPAO uptake ratio normalized to cerebellum was significantly decreased in older subjects, affecting both hemispheres. A slight left-to-right asymmetry was observed in HMPAO uptake of the whole study group. It did not, however, change with age. Regionally, both cortical and subcortical structures of older subjects were involved: uptake ratio to cerebellum was significantly lower (after correction for multiple testing) in the left basal ganglia and in the left superior temporal, right frontal and bilateral occipital cortices at 4 cm above the OML. At 6 cm above the OML, reduced uptake ratios were identified in the left frontal and bilateral parietal areas. At 7 cm, reduced uptake was detected in the right frontal and left occipital cortices. Most of these differences were reduced when uptake was normalized to whole slice, whereas an increase in uptake ratios was observed in the cingulate cortex of the elderly. An inverse correlation between age and HMPAO uptake ratios normalized to cerebellum was observed in a number of brain regions. These

Noninvasive imaging of experimental lung fibrosis.

Science.gov (United States)

Zhou, Yong; Chen, Huaping; Ambalavanan, Namasivayam; Liu, Gang; Antony, Veena B; Ding, Qiang; Nath, Hrudaya; Eary, Janet F; Thannickal, Victor J

2015-07-01

Small animal models of lung fibrosis are essential for unraveling the molecular mechanisms underlying human fibrotic lung diseases; additionally, they are useful for preclinical testing of candidate antifibrotic agents. The current end-point measures of experimental lung fibrosis involve labor-intensive histological and biochemical analyses. These measures fail to account for dynamic changes in the disease process in individual animals and are limited by the need for large numbers of animals for longitudinal studies. The emergence of noninvasive imaging technologies provides exciting opportunities to image lung fibrosis in live animals as often as needed and to longitudinally track the efficacy of novel antifibrotic compounds. Data obtained by noninvasive imaging provide complementary information to histological and biochemical measurements. In addition, the use of noninvasive imaging in animal studies reduces animal usage, thus satisfying animal welfare concerns. In this article, we review these new imaging modalities with the potential for evaluation of lung fibrosis in small animal models. Such techniques include micro-computed tomography (micro-CT), magnetic resonance imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and multimodal imaging systems including PET/CT and SPECT/CT. It is anticipated that noninvasive imaging will be increasingly used in animal models of fibrosis to gain insights into disease pathogenesis and as preclinical tools to assess drug efficacy.

Anti-GAD65 reactive peripheral blood mononuclear cells in the pathogenesis of cystic fibrosis related diabetes mellitus

Czech Academy of Sciences Publication Activity Database

Štechová, K.; Koloušková, S.; Sumnik, Z.; Cinek, O.; Kverka, Miloslav; Faresjo, M. K.; Chudoba, D.; Dovolilová, E.; Pechová, M.; Vrábelová, Z.; Böhmová, K.; Janeček, L.; Saudek, F.; Vavřinec, J.

2005-01-01

Roč. 38, č. 4 (2005), s. 319-323 ISSN 0891-6934 R&D Projects: GA MZd NR8127 Institutional research plan: CEZ:AV0Z50200510 Keywords : diabetes * cystic fibrosis * autoimmunity Subject RIV: EE - Microbiology, Virology Impact factor: 1.490, year: 2005

Protective role of NKT cells and macrophage M2-driven phenotype in bleomycin-induced pulmonary fibrosis.

Science.gov (United States)

Grabarz, Felipe; Aguiar, Cristhiane Favero; Correa-Costa, Matheus; Braga, Tárcio Teodoro; Hyane, Meire I; Andrade-Oliveira, Vinícius; Landgraf, Maristella Almeida; Câmara, Niels Olsen Saraiva

2018-04-01

Pulmonary fibrosis is a result of an abnormal wound healing in lung tissue triggered by an excessive accumulation of extracellular matrix proteins, loss of tissue elasticity, and debit of ventilatory function. NKT cells are a major source of Th1 and Th2 cytokines and may be crucial in the polarization of M1/M2 macrophages in pulmonary fibrogenesis. Although there appears to be constant scientific progress in that field, pulmonary fibrosis still exhibits no current cure. From these facts, we hypothesized that NKT cells could influence the development of pulmonary fibrosis via modulation of macrophage activation. Wild type (WT) and NKT type I cell-deficient mice (Jα18 -/- ) were subjected to the protocol of bleomycin-induced pulmonary fibrosis with or without treatment with NKT cell agonists α-galactosylceramide and sulfatide. The participation of different cell populations, collagen deposition, and protein levels of different cytokines involved in inflammation and fibrosis was evaluated. The results indicate a benign role of NKT cells in Jα18 -/- mice and in wild-type α-galactosylceramide-sulfatide-treated groups. These animals presented lower levels of collagen deposition, fibrogenic molecules such as TGF-β and vimentin and improved survival rates. In contrast, WT mice developed a Th2-driven response augmenting IL-4, 5, and 13 protein synthesis and increased collagen deposition. Furthermore, the arginase-1 metabolic pathway was downregulated in wild-type NKT-activated and knockout mice indicating lower activity of M2 macrophages in lung tissue. Hence, our data suggest that NKT cells play a protective role in this experimental model by down modulating the Th2 milieu, inhibiting M2 polarization and finally preventing fibrosis.

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

Directory of Open Access Journals (Sweden)

Mariana Zorrón Mei Hsia Pu

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

Management of the Upper Airway in Cystic Fibrosis

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Illing, Elisa A.; Woodworth, Bradford A.

2015-01-01

Purpose of Review Upper airway disease engenders significant morbidity for patients with cystic fibrosis and is increasingly recognized as having a much greater role in pulmonary outcomes and quality of life than originally believed. Widespread disparate therapeutic strategies for cystic fibrosis chronic rhinosinusitis underscore the absence of a standardized treatment paradigm. This review outlines the most recent evidence-based trends in the management of upper airway disease in cystic fibrosis. Recent Findings The unified airway theory proposes that the sinuses are a focus of initial bacterial colonization which seeds the lower airway and may play a large role in maintaining lung infections. Mounting evidence suggests more aggressive treatment of the sinuses may confer significant improvement in pulmonary disease and quality of life outcomes in cystic fibrosis patients. However, there is a lack of high-level evidence regarding medical and surgical management of cystic fibrosis chronic rhinosinusitis that makes generalizations difficult. Summary Well designed clinical trials with long-term follow-up concerning medical and surgical interventions for cystic fibrosis sinus disease are required to establish standardized treatment protocols, but increased interest in the sinuses as a bacterial reservoir for pulmonary infections has generated considerable attention. PMID:25250804

Cystic Fibrosis-Related Diabetes (CFRD): Daily Management

Science.gov (United States)

Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 This Web cast is supported by an unrestricted ... Moran, MD Professor, Pediatric Endocrinology University of Minnesota Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 ...

Vitamin K supplementation for cystic fibrosis.

Science.gov (United States)

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

2017-08-22

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

[Genetic counseling in cystic fibrosis].

Science.gov (United States)

Julia, S; Bieth, E

2000-08-01

Genetic counseling is an important part of health care in patients with cystic fibrosis or respiratory diseases associated with the CFTR (cystic fibrosis transmembrane conductance regulator) gene, including certain types of allergic bronchopulmonary aspergilloses or bronchial diseases (diffuse bronchiectasia). The basic goal is to provide patients with information on the transmission of cystic fibrosis and to asses the risk of recurrence. This risk is determined from molecular biology analyses examining the CFTR gene. Genotyping is the only means of screening for the heterozygous state, frequent in the French population (about 1/30). Because of the large number of mutated alleles not covered entirely by the genetic tests, there remains a question of probability expressed as a residual risk of a heterozygous state. A prenatal genotype diagnosis should be proposed to heterozygous couples who have a 25% risk of having a diseased child. Technically, this is almost always possible and the results are highly reliable. Nevertheless, there remains the risks related to sample taking and the ethical issue about which the patients must be informed. Management of these at risk couples who desire a child must be based on a multidisciplinary approach, particularly important when one of the parents has overt cystic fibrosis.

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)

Body fat assessed from body density and estimated from skinfold thickness in normal children and children with cystic fibrosis.

Science.gov (United States)

Johnston, J L; Leong, M S; Checkland, E G; Zuberbuhler, P C; Conger, P R; Quinney, H A

1988-12-01

Body density and skinfold thickness at four sites were measured in 140 normal boys, 168 normal girls, and 6 boys and 7 girls with cystic fibrosis, all aged 8-14 y. Prediction equations for the normal boys and girls for the estimation of body-fat content from skinfold measurements were derived from linear regression of body density vs the log of the sum of the skinfold thickness. The relationship between body density and the log of the sum of the skinfold measurements differed from normal for the boys and girls with cystic fibrosis because of their high body density even though their large residual volume was corrected for. However the sum of skinfold measurements in the children with cystic fibrosis did not differ from normal. Thus body fat percent of these children with cystic fibrosis was underestimated when calculated from body density and invalid when calculated from skinfold thickness.

Sleep Phase Delay in Cystic Fibrosis: A Potential New Manifestation of Cystic Fibrosis Transmembrane Regulator Dysfunction.

Science.gov (United States)

Jensen, Judy L; Jones, Christopher R; Kartsonaki, Christiana; Packer, Kristyn A; Adler, Frederick R; Liou, Theodore G

2017-08-01

Cystic fibrosis (CF) transmembrane regulator (CFTR) protein dysfunction causes CF. Improving survival allows detection of increasingly subtle disease manifestations. CFTR dysfunction in the central nervous system (CNS) may disturb circadian rhythm and thus sleep phase. We studied sleep in adults to better understand potential CNS CFTR dysfunction. We recruited participants from April 2012 through April 2015 and administered the Munich Chronotype Questionnaire (MCTQ). We compared free-day sleep measurements between CF and non-CF participants and investigated associations with CF survival predictors. We recruited 23 female and 22 male adults with CF aged 18 to 46 years and 26 female and 22 male volunteers aged 18 to 45 years. Compared with volunteers without CF, patients with CF had delayed sleep onset (0.612 h; P = .015), midsleep (1.11 h; P < .001), and wake (1.15 h; P < .001) times and prolonged sleep latency (7.21 min; P = .05) and duration (0.489 h; P = .05). Every hour delay in sleep onset was associated with shorter sleep duration by 0.29 h in patients with CF and 0.75 h in subjects without CF (P = .007) and longer sleep latency by 7.51 min in patients with CF and 1.6 min in volunteers without CF (P = .035). Among patients with CF, FEV 1 % predicted, prior acute pulmonary exacerbations, and weight were independent of all free-day sleep measurements. CF in adults is associated with marked delays in sleep phase consistent with circadian rhythm phase delays. Independence from disease characteristics predictive of survival suggests that sleep phase delay is a primary manifestation of CFTR dysfunction in the CNS. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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.

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

"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...

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.

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

Science.gov (United States)

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

2018-04-26

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

Secreted Klotho Attenuates Inflammation-Associated Aortic Valve Fibrosis in Senescence-Accelerated Mice P1.

Science.gov (United States)

Chen, Jianglei; Fan, Jun; Wang, Shirley; Sun, Zhongjie

2018-05-01

Senescence-accelerated mice P1 (SAMP1) is an aging model characterized by shortened lifespan and early signs of senescence. Klotho is an aging-suppressor gene. The purpose of this study is to investigate whether in vivo expression of secreted klotho ( Skl ) gene attenuates aortic valve fibrosis in SAMP1 mice. SAMP1 mice and age-matched (AKR/J) control mice were used. SAMP1 mice developed obvious fibrosis in aortic valves, namely fibrotic aortic valve disease. Serum level of Skl was decreased drastically in SAMP1 mice. Expression of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), F4/80, and CD68 was increased in aortic valves of SAMP1 mice, indicating inflammation. An increase in expression of α-smooth muscle actin (myofibroblast marker), transforming growth factorβ-1, and scleraxis (a transcription factor of collagen synthesis) was also found in aortic valves of SAMP1 mice, suggesting that accelerated aging is associated with myofibroblast transition and collagen gene activation. We constructed adeno-associated virus 2 carrying mouse Skl cDNA for in vivo expression of Skl. Skl gene delivery effectively increased serum Skl of SAMP1 mice to the control level. Skl gene delivery inhibited inflammation and myofibroblastic transition in aortic valves and attenuated fibrotic aortic valve disease in SAMP1 mice. It is concluded that senescence-related fibrotic aortic valve disease in SAMP1 mice is associated with a decrease in serum klotho leading to inflammation, including macrophage infiltration and transforming growth factorβ-1/scleraxis-driven myofibroblast differentiation in aortic valves. Restoration of serum Skl levels by adeno-associated virus 2 carrying mouse Skl cDNA effectively suppresses inflammation and myofibroblastic transition and attenuates aortic valve fibrosis. Skl may be a potential therapeutic target for fibrotic aortic valve disease. © 2018 American Heart Association, Inc.

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.

Cystic fibrosis Delta F508 heterozygotes, smoking, and reproduction

DEFF Research Database (Denmark)

Dahl, Morten; Tybjaerg-Hansen, A; Wittrup, H H

1998-01-01

Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is maintained at such a remarkably high incidence, however, it could be due to a reproductive advantage in cystic fibrosis heterozygotes. We tested this hypot......Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is maintained at such a remarkably high incidence, however, it could be due to a reproductive advantage in cystic fibrosis heterozygotes. We tested.......001). In conclusion, overall these results do not support a reproductive advantage for cystic fibrosis DeltaF508 heterozygotes. However, the data cannot totally exclude the possibility that nonsmoking DeltaF508 heterozygotes experience a reproductive advantage while smoking DeltaF508 heterozygotes experience...... the opposite, a reproductive disadvantage. Accordingly, the data suggest a previously undocumented role of smoking on fecundity among cystic fibrosis heterozygotes....

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.

Aging of Holocaust Survivors: Discrepancies Between Subjective and General Health in the greater Tel Aviv Area.

Science.gov (United States)

Ohana, Irit; Golander, Hava; Barak, Yoram

2018-04-01

Aging has been associated with perceived lowering of health, especially in post-traumatic individuals. The effects may be more complex or even different for Holocaust survivors as they age due to their inherited resilience and life perspective. A cross-sectional study was conducted of Holocaust survivors and a matched comparison group recruited from the general Israeli population. All participants underwent a personal interview and completed the Cumulative Illness Rating Scale and a survey of subjective Likert-scale questions about perceived health. The study comprised 214 older adults: 107 Holocaust survivors and 107 comparison participants; 101 women and 113 men. The mean age for the participants was 80.7 ± 4.7 years (range 68-93). Holocaust survivors did not differ from comparison subjects in general health measures (mean 51.50 ± 3.06 vs. 52.27 ± 3.24, respectively). However, the Holocaust survivors' subjective health was significantly lower, F (2,211) = 4.18, P Holocaust survivors to achieve successful aging.

Liver Disease in Cystic Fibrosis: an Update

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

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

2016-09-01

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

Fibrosis imaging : Current concepts and future directions

NARCIS (Netherlands)

Baues, Maike; Dasgupta, Anshuman; Ehling, Josef; Prakash, Jai; Boor, Peter; Tacke, Frank; Kiessling, Fabian; Lammers, Twan

2017-01-01

Fibrosis plays an important role in many different pathologies. It results from tissue injury, chronic inflammation, autoimmune reactions and genetic alterations, and it is characterized by the excessive deposition of extracellular matrix components. Biopsies are routinely employed for fibrosis

Cystic fibrosis with normal sweat chloride concentration: case report

Directory of Open Access Journals (Sweden)

Silva Filho Luiz Vicente Ferreira da

2003-01-01

Full Text Available Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.

Clinical Meaning of Ascites in Patients with Endomyocardial Fibrosis

Directory of Open Access Journals (Sweden)

Barretto Antonio Carlos Pereira

2002-01-01

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

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.

Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.

Directory of Open Access Journals (Sweden)

Jody Groenendyk

Full Text Available Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function.We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER homeostasis, transient activation of the unfolded protein response (UPR pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA is sufficient to prevent cardiac fibrosis, and improved exercise tolerance.We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function.

Self-management education for cystic fibrosis.

LENUS (Irish Health Repository)

Savage, Eileen

2011-01-01

Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to manage the effects of illness on their lives. Although self-management education interventions have been developed for cystic fibrosis, no previous systematic review of the evidence of effectiveness of these interventions has been conducted.

Effects and mechanisms of pirfenidone, prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models.

Science.gov (United States)

Yu, Wencheng; Guo, Fang; Song, Xiaoxia

2017-12-01

Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown. This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF. Rat IPF model was established by endotracheal injection of 5 mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100 mg/kg once daily), prednisone (H, 5 mg/kg once daily) and acetylcysteine (N, 4 mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay. After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p fibrosis scores of lung tissues, as well as expression of TGF-β1, TNF-α and PDGF, but the expression of Cav-1 was higher (p fibrosis score was significantly lower and the protein expression of Cav-1 was significantly higher in the P group (p fibrosis scores (r = -0.506, p pulmonary fibrosis in rat IPF models, which may be related with enhanced caveolin-1, reduced TNF-α, TGF-β1, PDGF.

Left ventricular remodeling and fibrosis: Sex differences and relationship with diastolic function in hypertrophic cardiomyopathy

International Nuclear Information System (INIS)

Chen, You-Zhou; Qiao, Shu-Bin; Hu, Feng-Huan; Yuan, Jian-Song; Yang, Wei-Xian; Cui, Jin-Gang; Zhang, Yan; Zhang, Chang-Lin

2015-01-01

Highlights: • There are significant differences in LV remodeling and fibrosis as divided by sex. • Women have worse diastolic dysfunction compared to men measured by CMR. • LV remodeling and fibrosis correlate with markers of diastolic dysfunction. - Abstract: Objectives: We investigated sex differences in left ventricular (LV) remodeling and fibrosis and their relationship with LV diastolic dysfunction by cardiovascular magnetic resonance (CMR). Methods: CMR imaging was performed simultaneously in 152 age-matched patients (76 men, 76 women; mean age: 49 ± 9 years) without LV systolic dysfunction. LV remodeling index (LVRI) was calculated as the ratio of LV mass and end-diastolic volume. Diastolic function indexes including peak filling rate (PFR) and time to PFR (tPFR) were evaluated. Extent of late gadolinium enhancement (LGE) was measured. Results: LVRI and extent of LGE were greater in women compared with men (1.48 ± 0.22 vs. 1.36 ± 0.28 g/ml; 13.15 ± 2.48 vs. 11.35 ± 2.34 g, respectively, both P < 0.001). Women had lower PFR and higher tPFR (both P < 0.001) than men. LVRI and the extent of LGE showed significant relationships with parameters of diastolic function in both sex. In a multivariate analysis, LVRI remained a strong independent predictor of PFR and TPFR in women (β = −0.272, P = 0.032; β = 0.348, P = 0.016, respectively), and in men (β = −0.374, P < 0.001; β = 0.660, P < 0.001, respectively). Furthermore, the extent of LGE also remained an independent predictor of PFR in women (β = −0.283, P = 0.033) and men (β = −0.492, P < 0.001). Conclusions: There are prominent sex differences in LV remodeling and myocardial fibrosis. We suggest that the effects of LV remodeling and fibrosis may lead to diastolic dysfunction with greater susceptibility to worse clinical outcome in women

Left ventricular remodeling and fibrosis: Sex differences and relationship with diastolic function in hypertrophic cardiomyopathy

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Chen, You-Zhou [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Qiao, Shu-Bin, E-mail: qsbfw@sina.com [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Hu, Feng-Huan; Yuan, Jian-Song; Yang, Wei-Xian; Cui, Jin-Gang [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Yan [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Chang-Lin [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

2015-08-15

Highlights: • There are significant differences in LV remodeling and fibrosis as divided by sex. • Women have worse diastolic dysfunction compared to men measured by CMR. • LV remodeling and fibrosis correlate with markers of diastolic dysfunction. - Abstract: Objectives: We investigated sex differences in left ventricular (LV) remodeling and fibrosis and their relationship with LV diastolic dysfunction by cardiovascular magnetic resonance (CMR). Methods: CMR imaging was performed simultaneously in 152 age-matched patients (76 men, 76 women; mean age: 49 ± 9 years) without LV systolic dysfunction. LV remodeling index (LVRI) was calculated as the ratio of LV mass and end-diastolic volume. Diastolic function indexes including peak filling rate (PFR) and time to PFR (tPFR) were evaluated. Extent of late gadolinium enhancement (LGE) was measured. Results: LVRI and extent of LGE were greater in women compared with men (1.48 ± 0.22 vs. 1.36 ± 0.28 g/ml; 13.15 ± 2.48 vs. 11.35 ± 2.34 g, respectively, both P < 0.001). Women had lower PFR and higher tPFR (both P < 0.001) than men. LVRI and the extent of LGE showed significant relationships with parameters of diastolic function in both sex. In a multivariate analysis, LVRI remained a strong independent predictor of PFR and TPFR in women (β = −0.272, P = 0.032; β = 0.348, P = 0.016, respectively), and in men (β = −0.374, P < 0.001; β = 0.660, P < 0.001, respectively). Furthermore, the extent of LGE also remained an independent predictor of PFR in women (β = −0.283, P = 0.033) and men (β = −0.492, P < 0.001). Conclusions: There are prominent sex differences in LV remodeling and myocardial fibrosis. We suggest that the effects of LV remodeling and fibrosis may lead to diastolic dysfunction with greater susceptibility to worse clinical outcome in women.

Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis

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Knudsen, K. B.; Pressler, T.; Mortensen, L. H.

2016-01-01

Background: Cystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study...... was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF.Methods: We administered three standardized questionnaires to 67 patients with CF aged 18–30 years; Morisky Medication Adherence Scale, Major...

Prenatal diagnosis of meconium ileus and meconium peritonitis: Indications for cystic fibrosis testing

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Egić Amira

2011-01-01

Full Text Available Introduction. More recently, the regions of increased abdominal echogenicity such as echogenic bowel, meconium ileus and meconium peritonitis have been associated with an increased prevalence of a variety of unfavourable outcomes including chromosomal abnormalities, cytomegalovirus infection, intestinal obstruction, anorectal malformations and cystic fibrosis. Earlier prenatal examinations of these severe autosomal recessive diseases had been suggested only to families with history of cystic fibrosis. Recently, systemic examination has been introduced by ultrasound with bowel hyperechogenicity where the fetus is the index case for genetic disease. Risk for cystic fibrosis with this ultrasonography findings ranges from 0-33%. Outline of Cases. Two patients are presented, aged 24 and 29 years, both primigravide. The first one had ultrasonography finding of meconium peritonitis revealed at the 37th week of gestation and the other meconium ileus revealed on ultrasonography at the 29th week of gestation. Both patients had prenatal testing of foetal blood obtained by cordocenthesis, both had normal kariotype and were negative for cytomegalovirus infection. Parental DNA testing for the 2nd patient showed that parents were not carriers for the 29 most frequent mutations. Both neonates had intestinal obstruction, underwent surgery and early postoperative course was normal. Hystopathological finding suggested a possibility of cystic fibrosis for the 1st patient, but parents did not want to be tested and for the 2nd one congenital bowel stenosis as a cause of intestinal obstruction. Conclusion. Ultrasonographic echogenic bowel is an indication for invasive procedures for foetal blood testing for chromosomal abnormalities, congenital infections and parental testing for cystic fibrosis. Only if parental heterozygosity is proven foetus should be tested.

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

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

2016-03-01

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

Repeatability of Computerized Tomography-Based Anthropomorphic Measurements of Frailty in Patients With Pulmonary Fibrosis Undergoing Lung Transplantation.

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McClellan, Taylor; Allen, Brian C; Kappus, Matthew; Bhatti, Lubna; Dafalla, Randa A; Snyder, Laurie D; Bashir, Mustafa R

To determine interreader and intrareader repeatability and correlations among measurements of computerized tomography-based anthropomorphic measurements in patients with pulmonary fibrosis undergoing lung transplantation. This was an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study of 23 randomly selected subjects (19 male and 4 female; median age = 69 years; range: 66-77 years) with idiopathic pulmonary fibrosis undergoing pulmonary transplantation, who had also undergone preoperative thoracoabdominal computerized tomography. Five readers of varying imaging experience independently performed the following cross-sectional area measurements at the inferior endplate of the L3 vertebral body: right and left psoas muscles, right and left paraspinal muscles, total abdominal musculature, and visceral and subcutaneous fat. The following measurements were obtained at the inferior endplate of T6: right and left paraspinal muscles with and without including the trapezius muscles and subcutaneous fat. Three readers repeated all measurements to assess intrareader repeatability. Intrareader repeatability was nearly perfect (interclass correlation coefficients = 0.99, P < 0.001). Interreader agreement was excellent across all 5 readers (interclass correlation coefficients: 0.71-0.99, P < 0.001). Coefficients of variance between measures ranged from 3.2%-6.8% for abdominal measurements, but were higher for thoracic measurements, up to 23.9%. Correlation between total paraspinal and total psoas muscle area was strong (r 2 = 0.67, P < 0.001). Thoracic and abdominal musculature had a weaker correlation (r 2 = 0.35-0.38, P < 0.001). Measures of thoracic and abdominal muscle and fat area are highly repeatable in patients with pulmonary fibrosis undergoing lung transplantation. Measures of muscle area are strongly correlated among abdominal locations, but inversely correlated between abdominal and thoracic locations

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

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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.

Endocytosis and intracellular protein degradation in cystic fibrosis fibroblasts

International Nuclear Information System (INIS)

Jessup, W.; Dean, R.T.

1983-01-01

Normal rates of pinocytosis of [ 3 H]sucrose were measured in cystic fibrosis fibroblasts, and were not affected by the addition of cystic fibrosis serum. Bulk protein degradation (a significant proportion of which occurs intralysosomally following autophagy) and its regulation by growth state were apparently identical in normal and cystic fibrosis cultures. (Auth.)

Microbiological surveillance in patients with cystic fibrosis

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Paola Gualdi

2010-06-01

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

The Bourne Tragedy:
Lost Subjects of the Bioconvergent Age

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Debbie Epstein

2011-10-01

Full Text Available This paper examines the Bourne trilogy to explore several characteristics of what we term the bioconvergent age. First, we consider the imagined and actual interfaces of bioconvergence—of body, gadgetry, and electronic communications. We explore the ways in which the bioconvergent tendencies represented in and by Bourne reflect and cultivate a cultural unconscious deeply seduced by and imbricated in surveillant governmentality. Second, we consider the ways in which the trilogy achieves its effects through the deployment of both hyperrealism and verisimilitude. In this context, we explore the filmic interpellation of audiences into a fantasy of omnipotence and omni-science, on the one hand, and the underlying phantasy of a zero-sum world that uncouples morality from affect, on the other. Thus, we consider the ways in which Bourne articulates two interlinked phenomena—a distinctively American romance with the sociopathic/heroic subject and a paranoid, dystopic world that is and seems seductively real. Our third theme is the Bourne journey through an obsessional spiral of paranoia, action, and reaction. Here we explore the trilogy as a social description of the expulsive and retentive tendencies of the bioconvergent age, where the demand for instantaneity drives out all other considerations (morality, reason, connection and where the lost subject, in his interminable quest for himself, remains lost.