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Noninvasive Markers (noninvasive + marker)
Selected AbstractsNoninvasive markers of esophageal varices: Another round, not the last,HEPATOLOGY, Issue 1 2004Gennaro D'Amico First page of article [source] Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studiesCLINICAL & EXPERIMENTAL ALLERGY, Issue 4 2009P. G. Gibson Prof. Summary Background Current asthma guidelines recommend treatment based on the assessment of asthma control using symptoms and lung function. Noninvasive markers are an attractive way to modify therapy since they offer improvedselection of active treatment(s) based on individual response, and improvedtitration of treatment using markers that are better related to treatment outcomes. Aims: To review the methodological and design features of noninvasive marker studies in asthma. Methods Systematic assessment of published randomized trials of asthma therapy guided by fraction of exhaled nitric oxide(FENO). Results FENO has appeal as a marker to adjust asthma therapy since it is readily measured, gives reproducible results, and is responsive to changes in inhaled corticosteroid doses. However, the five randomised trials of FENO guided therapy have had mixed results. This may be because there are specific design and methodological issues that need to be addressed in the conduct of ASthma TReatment ALgorithm(ASTRAL) studies. There needs to be a clear dose response relationship for the active drugs used and the outcomes measured. The algorithm decision points should be based on outcomes in the population of interest rather than the range of values in healthy people, and the algorithm used needs to provide a sufficiently different result to clinical decision making in order for there to be any discernible benefit. A new metric is required to assess the algorithm performance, and the discordance:concordance(DC) ratio can assist with this. Conclusion Incorporating these design features into future FENO studies should improve the study performance and aid in obtaining a better estimate of the value of FENO guided asthma therapy. [source] Inferior Vena Cava Percentage Collapse During Respiration Is Affected by the Sampling Location: An Ultrasound Study in Healthy VolunteersACADEMIC EMERGENCY MEDICINE, Issue 1 2010David J. Wallace MD Abstract Objectives:, Physicians are unable to reliably determine intravascular volume status through the clinical examination. Respiratory variation in the diameter of the inferior vena cava (IVC) has been investigated as a noninvasive marker of intravascular volume status; however, there has been a lack of standardization across investigations. The authors evaluated three locations along the IVC to determine if there is clinical equivalence of the respiratory percent collapse at these sites. The objective of this study was to determine the importance of location when measuring the IVC diameter during quiet respiration. Methods:, Measurements of the IVC were obtained during quiet passive respiration in supine healthy volunteers. All images were recorded in B-mode, with cine-loop adjustments in real time, to ensure that maximum and minimum IVC dimensions were obtained. One-way repeated-measures analysis of variance (ANOVA) was used for comparison of IVC measurement sites. Results:, The mean (±SD) percentage collapse was 20% (±16%) at the level of the diaphragm, 30% (±21%) at the level of the hepatic vein inlet, and 35% (±22%) at the level of the left renal vein. ANOVA revealed a significant overall effect for location of measurement, with F(2,35) = 6.00 and p = 0.006. Contrasts showed that the diaphragm percentage collapse was significantly smaller than the hepatic (F(1,36) = 5.14; p = 0.03) or renal caval index (F(1,36) = 11.85; p = 0.002). Conclusions:, Measurements of respiratory variation in IVC collapse in healthy volunteers are equivalent at the level of the left renal vein and at 2 cm caudal to the hepatic vein inlet. Measurements taken at the junction of the right atrium and IVC are not equivalent to the other sites; clinicians should avoid measuring percentage collapse of the IVC at this location. ACADEMIC EMERGENCY MEDICINE 2010; 17:96,99 © 2009 by the Society for Academic Emergency Medicine [source] Reliability of a new hand-held device for the measurement of exhaled nitric oxideALLERGY, Issue 10 2007B. Khalili Background:, Given the importance of airway inflammation in asthma, there has been an effort to incorporate inflammatory markers into its management. Measurement of fractional exhaled nitric oxide (FeNO) is a noninvasive marker of airway inflammation; however, the use of the available FeNO analyzer is limited by several factors including its cost and lack of transportability. The aim of this study was to compare the performance of a new hand-held FeNO measuring device (NIOX MINO) to the current clinical standard , the chemiluminescence FeNO analyzer (NIOX). Methods:, Subjects 6 years and older presenting to an allergy and asthma clinic underwent FeNO evaluation by NIOX and each of three NIOX MINOs. The mean of two acceptable measurements from the NIOX and the first approved measurement from each NIOX MINO were used for analysis. Results:, One hundred ten patients aged 6,86 years completed the study. Intrasubject FeNO levels obtained by each of the three NIOX MINOs revealed no significant difference between the measurements (P = 0.59). There was a very strong correlation between FeNO measurements by NIOX and by NIOX MINO (r = 0.98, P < 0.0001). The mean intrasubject FeNO difference between NIOX and NIOX MINO was ,0.5 p.p.b. which was not statistically significantly different from zero (P = 0.21). Conclusions:, Fractional exhaled nitric oxide measurements by the NIOX MINO showed a strong correlation and a high degree of agreement with the current standard stationary device. The NIOX MINO may be reliably used in clinical practice. [source] Leukotriene synthesis during respiratory syncytial virus bronchiolitis: Influence of age and atopy,PEDIATRIC PULMONOLOGY, Issue 4 2005Giovanni Piedimonte MD Abstract Respiratory syncytial virus (RSV) infection is the most common cause of bronchiolitis in infants and an important risk factor for the development of recurrent wheezing and asthma. Cysteinyl leukotrienes were implicated in the pathophysiology of these diseases, and are being targeted for their diagnosis and therapy. We measured urinary leukotriene E4 (LTE4) in infants with RSV bronchiolitis in comparison with controls without respiratory infection, and investigated whether medical and family history, age, and passive exposure to tobacco smoke are related to urinary leukotriene excretion. We studied 33 infants with bronchiolitis and 25 controls, 1,12 months of age. Demographic and historical data were obtained from informed-consent forms and questionnaires completed by the parents. RSV was detected in nasal secretions by enzyme-linked immunoassay. Urine samples were collected on day of admission and were analyzed for LTE4 with an enzyme-linked immunoassay. Urinary LTE4 was 8-fold higher in infants with bronchiolitis than in controls. Leukotriene excretion was significantly higher in infected infants <6 months of age with a medical history of eczema or dry cough and/or family history of asthma. Multivariate analysis revealed that eczema and dry cough are independently associated with high LTE4 excretion during bronchiolitis. Exposure to tobacco smoke did not affect urinary LTE4. Our study shows that leukotriene synthesis during bronchiolitis is particularly elevated in younger infants with an atopic/asthmatic background. Urinary LTE4 may become a valuable, noninvasive marker for the identification of patients who will benefit most from therapy with leukotriene modifiers for management of bronchiolitis. Pediatr Pulmonol. © 2005 Wiley-Liss, Inc. [source] Kidney Injury Molecule-1 is an Early Noninvasive Indicator for Donor Brain Death-Induced Injury Prior to Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009W. N. Nijboer With more marginal deceased donors affecting graft viability, there is a need for specific parameters to assess kidney graft quality at the time of organ procurement in the deceased donor. Recently, kidney injury molecule-1 (Kim-1) was described as an early biomarker of renal proximal tubular damage. We assessed Kim-1 in a small animal brain death model as an early and noninvasive marker for donor-derived injury related to brain death and its sequelae, with subsequent confirmation in human donors. In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In human donors, 2.5-fold kidney injury molecule-1 (KIM-1) gene upregulation and 2-fold higher urine levels were found in donation after brain death (DBD) donors compared to living kidney donors. Multiple regression analysis showed that urinary KIM-1 at brain death diagnosis was a positive predictor of recipient serum creatinine, 14 days (p < 0.001) and 1 year (p < 0.05) after kidney transplantation. In conclusion, we think that Kim-1 is a promising novel marker for the early, organ specific and noninvasive detection of brain death-induced donor kidney damage. [source] Microvolt T-Wave Alternans during Holter Monitoring in Children and AdolescentsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2010Leonid Makarov M.D. Background: Time-domain microvolt T-wave alternans (TWA) has been described as a noninvasive marker of sudden cardiac death in adults. The incidence of TWA in pediatric populations has not been defined well. The aim of the study was to determine peculiarities of TWA in children. Methods: We examined 68 healthy patients,newborns (20) and children in age group of 7,17 years (48),and 85 pediatric patients: ventricular premature beats,65; dilated cardiomyopathy (DCMP),2; long QT syndrome (LQTS),10; Brugada syndrome (BrS),5, catecholaminergic ventricular tachycardia (CVT),3. All underwent Holter monitoring (HM) with definition of the peak value of TWA by modified moving average method. Results: In healthy newborns, TWA was 32 ± 8 (12,55) ,V (HR 123,156 bmp). In healthy children (7,17 years) it was 30 ± 11 (10,l 55) ,V, (HR 64,132 bmp) without any differences between boys and girls. In all group of patients, TWA were significantly higher (P < 0.05) than in healthy. Circadian peak of TWA was found (90%) in a second part of day and at sleep (8%). Among them 60% (LQTS, BrS, and DCPM) had TWA > 55 ,V. Conclusion: Time-domain TWA during HM in children was independent of age, gender, and heart rate. In 94% healthy children, values of TWA do not exceed 55 ,V but 20,50% children with cardiac pathology had TWA more than 55 ,V. Night circadian type of TWA in diseases with risk of life-threatening arrhythmias associated with TWA was more than 55 ,V. Ann Noninvasive Electrocardiol 2010;15(2):138,144 [source] The Role of Exhaled Nitric Oxide in Evaluation of Acute Asthma in a Pediatric Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 1 2009Maria Y. Kwok MD Abstract Objectives:, Fractional excretion of nitric oxide (FENO) has been used as a noninvasive marker to assess and manage chronic asthma in adults and children. The aim of this study was to determine the feasibility of obtaining FENO concentrations in children treated in the emergency department (ED) for acute asthma exacerbation and to examine the association between FENO concentrations and other measures of acute asthma severity. Methods:, This was a cross-sectional study of a convenience sample of children 2,18 years old who were seen in an urban ED for acute asthma exacerbation. Using a tidal breathing method with real-time display, the authors measured FENO concentrations before and 1 hour after the administration of corticosteroids and at discharge from the ED. Outcome measures included pulmonary index score (PIS), hospital admission, and short-term outcomes (e.g., missed days of school). Results:, A total of 133 subjects were enrolled. Sixty-eight percent (95% confidence interval [CI] = 60% to 76%) of the subjects provided adequate breaths for FENO measurement. There was no difference in the median initial FENO concentration among subjects, regardless of the severity of their acute asthma. Most subjects showed no change in their FENO concentrations from the start to the end of treatment. FENO concentrations were not significantly associated with other short-term outcomes. Conclusions:, Measurement of FENO is difficult for a large proportion of children with acute asthma exacerbation. FENO concentration during an asthma exacerbation does not correlate with other measures of acute severity and has limited utility in the ED management of acute asthma in children. [source] High levels and gender difference of exhaled nitric oxide in Chinese schoolchildrenCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2005G. W. K. Wong Summary Background Exhaled nitric oxide (eNO) may represent a useful noninvasive marker of airway inflammation, but data on the reference population values in schoolchildren are limited. No reference eNO study in Asian children has been published. Methods Levels of eNO in a sample of 531 schoolchildren aged 11,18 years recruited from five schools (three international schools) in Hong Kong were measured online by a chemiluminescence analyser according to ERS/ATS standard. Each student also completed an International Study of Asthma and Allergic disease in Childhood questionnaire. Results Among the children without a physician's diagnosis of asthma or symptoms of wheeze, rhinitis and eczema, there were 258 Chinese and 33 Caucasians. In control Chinese children, the eNO level (median: interquantile range) was significantly higher (P<0.001) in males (17.0 parts per billion (p.p.b.); 10.7,36.6) than in females (10.8 p.p.b.; 7.8,17.6). When compared with Caucasian control males (11.6 p.p.b.; 8.2,19.3) and females (9.1 p.p.b.; 7.5,11.9), the Chinese children had significantly higher eNO levels for both males (P=0.011) and females (P=0.037). For Chinese asthmatic males, the median eNO (interquartile range) was 39.8 p.p.b. (12.5,73.8), and for asthmatic females, 18.0 (9.6,56.3). After controlling for sex in Chinese controls, eNO did not have any significant correlation with height, weight and body mass index or body surface area. Conclusions This study demonstrates a gender difference of eNO level in healthy Chinese schoolchildren. When compared with Caucasians, Chinese children have significantly higher eNO levels. [source] SAFE biopsy: A validated method for large-scale staging of liver fibrosis in chronic hepatitis C,HEPATOLOGY, Issue 6 2009Giada Sebastiani The staging of liver fibrosis is pivotal for defining the prognosis and indications for therapy in hepatitis C. Although liver biopsy remains the gold standard, several noninvasive methods are under evaluation for clinical use. The aim of this study was to validate the recently described sequential algorithm for fibrosis evaluation (SAFE) biopsy, which detects significant fibrosis (,F2 by METAVIR) and cirrhosis (F4) by combining the AST-to-platelet ratio index and Fibrotest-Fibrosure, thereby limiting liver biopsy to cases not adequately classifiable by noninvasive markers. Hepatitis C virus (HCV) patients (2035) were enrolled in nine locations in Europe and the United States. The diagnostic accuracy of SAFE biopsy versus histology, which is the gold standard, was investigated. The reduction in the need for liver biopsies achieved with SAFE biopsy was also assessed. SAFE biopsy identified significant fibrosis with 90.1% accuracy (area under the receiver operating characteristic curve = 0.89; 95% confidence interval, 0.87-0.90) and reduced by 46.5% the number of liver biopsies needed. SAFE biopsy had 92.5% accuracy (area under the receiver operating characteristic curve = 0.92; 95% confidence interval, 0.89-0.94) for the detection of cirrhosis, obviating 81.5% of liver biopsies. A third algorithm identified significant fibrosis and cirrhosis simultaneously with high accuracy and a 36% reduction in the need for liver biopsy. The patient's age and body mass index influenced the performance of SAFE biopsy, which was improved with adjusted Fibrotest-Fibrosure cutoffs. Two hundred two cases (9.9%) had discordant results for significant fibrosis with SAFE biopsy versus histology, whereas 153 cases (7.5%) were discordant for cirrhosis detection; 71 of the former cases and 56 of the latter cases had a Fibroscan measurement within 2 months of histological evaluation. Fibroscan confirmed SAFE biopsy findings in 83.1% and 75%, respectively. Conclusion: SAFE biopsy is a rational and validated method for staging liver fibrosis in hepatitis C with a marked reduction in the need for liver biopsy. It is an attractive tool for large-scale screening of HCV carriers. (HEPATOLOGY 2009.) [source] Platelet count is not a predictor of the presence or development of gastroesophageal varices in cirrhosis,HEPATOLOGY, Issue 1 2008Amir A. Qamar Current guidelines recommend esophagogastroduodenoscopy (EGD) in patients with cirrhosis to screen for gastroesophageal varices (GEV). Thrombocytopenia has been proposed as a noninvasive test to predict the presence of GEV. There is no agreement regarding a specific platelet count (PLT) that can reliably predict GEV. The present longitudinal study aims to (1) further investigate the relationship between varices and PLT at the time of endoscopy, (2) investigate whether changes in PLT from the baseline over time can predict the development of GEV, and (3) investigate whether changes in PLT correlate with the hepatic venous pressure gradient (HVPG). A secondary analysis was conducted for 213 subjects with compensated cirrhosis with portal hypertension but without GEV enrolled in a randomized, placebo-controlled, double-blind trial of a nonselective beta-blocker used to prevent GEV. PLTs were obtained every 3 months, and HVPG measurements and EGD were done annually. The PLTs were compared between subjects who did and did not develop GEV. In a median follow-up of 54.9 months, 84 patients developed GEV. PLT was greater than 150,000 in 15% of patients at the development of GEV. A receiver operating curve did not show any PLT with high sensitivity or specificity for the presence of GEV. Subjects with clinically insignificant portal hypertension (HVPG < 10 mm Hg) whose PLT remained greater than 100,000 had a 2-fold reduction in the occurrence of GEV (P = 0.0374). A significant correlation was found between HVPG and PLT at the baseline, year 1, and year 5 (P < 0.0001). Conclusion: Cross-sectional or longitudinal evaluations of PLTs are inadequate noninvasive markers for GEV. Patients with mild portal hypertension whose PLT remains greater than 100,000 have significantly less risk of GEV. Although HVPG correlates somewhat with PLT, changes in PLT cannot be used as a surrogate for HVPG changes. (HEPATOLOGY 2008;47:153,159.) [source] Ulcerative colitis: Correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytesINFLAMMATORY BOWEL DISEASES, Issue 12 2009Alain M. Schoepfer MD Abstract Background: The accuracy of noninvasive markers for the detection of endoscopically active ulcerative colitis (UC) according the Rachmilewitz Score is so far unknown. The aim was to evaluate the correlation between endoscopic disease activity and fecal calprotectin, Clinical Activity Index, C-reactive protein (CRP), and blood leukocytes. Methods: UC patients undergoing colonoscopy were prospectively enrolled and scored independently according the endoscopic and clinical part of the Rachmilewitz Index. Patients and controls provided fecal and blood samples for measuring calprotectin, CRP, and leukocytes. Results: Values in UC patients (n = 134) compared to controls (n = 48): calprotectin: 396 ± 351 versus 18.1 ± 5 ,g/g, CRP 16 ± 13 versus 3 ± 2 mg/L, blood leukocytes 9.9 ± 3.5 versus 5.4 ± 1.9 g/L (all P < 0.001). Endoscopic disease activity correlated closest with calprotectin (Spearman's rank correlation coefficient r = 0.834), followed by Clinical Activity Index (r = 0.672), CRP (r = 0.503), and leukocytes (r = 0.461). Calprotectin levels were significantly lower in UC patients with inactive disease (endoscopic score 0,3, calprotectin 42 ± 38 ,g/g), compared to patients with mild (score 4,6, calprotectin 210 ± 121 ,g/g, P < 0.001), moderate (score 7,9, calprotectin 392 ± 246 ,g/g, P = 0.002), and severe disease (score 10,12, calprotectin 730 ± 291 ,g/g, P < 0.001). The overall accuracy for the detection of endoscopically active disease (score ,4) was 89% for calprotectin, 73% for Clinical Activity Index, 62% for elevated CRP, and 60% for leukocytosis. Conclusions: Fecal calprotectin correlated closest with endoscopic disease activity, followed by Clinical Activity Index, CRP, and blood leukocytes. Furthermore, fecal calprotectin was the only marker that reliably discriminated inactive from mild, moderate, and highly active disease, which emphasizes its usefulness for activity monitoring. Inflamm Bowel Dis 2009 [source] Fecal S100A12 and fecal calprotectin as noninvasive markers for inflammatory bowel disease in childrenINFLAMMATORY BOWEL DISEASES, Issue 3 2008Marc A. Sidler MD Abstract Background: Fecal calprotectin is a sensitive marker for gut inflammation. Recently, we have established that a related protein, S100A12, is elevated in the feces of children with inflammatory bowel disease (IBD). This may represent a specific and sensitive disease marker. The objective was to investigate the utility of fecal S100A12, in comparison to fecal calprotectin and standard inflammatory markers, as a screening marker for IBD in children with gastrointestinal symptoms. Methods: Stool samples were obtained from 61 children presenting with gastrointestinal symptoms requiring endoscopy. Fecal S100A12, calprotectin, and serum S100A12 levels were measured and correlated to final diagnosis and standard tests (ESR, CRP, platelet count, and albumin). Results: Children diagnosed with IBD (n = 31) had elevated fecal S100A12 (median 55.2 mg/kg) and calprotectin (median 1265 mg/kg) levels compared with the children without IBD (n = 30; S100A12: median 1.1 mg/kg, P < 0.0001; calprotectin: median 30.5 mg/kg; P < 0.0001). The sensitivity and specificity of fecal S100A12 (cutoff 10 mg/kg) for the detection of IBD were both 97%, whereas fecal calprotectin (cutoff 50 mg/kg) gave a sensitivity of 100% and a specificity of 67%. Conclusions: Both fecal markers were superior to the sensitivities and specificities of any standard inflammatory test. Both fecal S100A12 and calprotectin are sensitive markers of gastrointestinal inflammation, but fecal S100A12 provided exceptional specificity in distinguishing children with IBD from children without IBD. Fecal S100A12 is a simple, noninvasive test that can be used to screen and select children warranting further invasive and laborious procedures such as endoscopy for the investigation of their gastrointestinal symptoms. (Inflamm Bowel Dis 2007) [source] Dementia and Alzheimer's Disease Incidence in Relationship to Cardiovascular Disease in the Cardiovascular Health Study CohortJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2005Anne B. Newman MD Objectives: To determine whether coronary artery disease, peripheral arterial disease (PAD), or noninvasive markers of cardiovascular disease (CVD) predict the onset of dementia and Alzheimer's disease (AD). Design: Longitudinal cohort study. Setting: Four U.S. communities. Participants: Men and women (N=3,602) with a brain magnetic resonance imaging (MRI) scan but no dementia were followed for 5.4 years. Participants with stroke were excluded. Measurements: Neurologists and psychiatrists classified incident cases of dementia and subtype using neuropsychological tests, examination, medical records and informant interviews. CVD was defined at the time of the MRI scan. Noninvasive tests of CVD were assessed within 1 year of the MRI. Apolipoprotein E allele status, age, race, sex, education, Mini-Mental State Examination score, and income were assessed as potential confounders. Results: The incidence of dementia was higher in those with prevalent CVD, particularly in the subgroup with PAD. The rate of AD was 34.4 per 1,000 person-years for those with a history of CVD, versus 22.2 per 1,000 person-years without a history of CVD (adjusted hazard ratio (HR)=1.3, 95% confidence interval (CI)=1.0,1.7). Rates of AD were highest in those with PAD (57.4 vs 23.7 per 100 person-years, adjusted HR=2.4, 95% CI=1.4,4.2). Results were similar with further exclusion of those with vascular dementia from the AD group. A gradient of increasing risk was noted with the extent of vascular disease. Conclusion: Older adults with CVD other than stroke had a higher risk of dementia and AD than did those without CVD. The risk was highest in people with PAD, suggesting that extensive peripheral atherosclerosis is a risk factor for AD. [source] Optimal combinations of ultrasound-based and serum markers of disease severity in patients with chronic hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 8 2010J. F. L. Cobbold Summary., Combinations of noninvasive markers may improve discrimination of chronic liver disease severity. The aims of this study were to compare four validated serum and ultrasound-based markers of hepatic disease severity head-to-head with liver biopsy and to assess optimal combinations with consideration of cost. A total of 67 patients with biopsy-proven chronic hepatitis C underwent all four techniques on the same visit [aspartate aminotransferase (AST) to platelet ratio index (APRI); Enhanced Liver Fibrosis (ELF) panel; transient elastography (TE) and ultrasound microbubble hepatic transit times (HTT)]. Markers were combined according to increasing financial cost and ordinal regression used to determine contributions. APRI, ELF, TE and HTT predicted cirrhosis with diagnostic accuracy of 86%, 91%, 90% and 83% respectively. ELF and TE were the most reliable tests with an intra-class correlation of 0.94 each. Either ELF or TE significantly enhanced the prediction of fibrosis stage when combined with APRI, but when combined together, did not improve the model further. Addition of third or fourth markers did not significantly improve prediction of fibrosis. Combination of APRI with either ELF or TE effectively predicts fibrosis stage, but combinations of three or more tests lead to redundancy of information and increased cost. [source] Prediction of significant liver fibrosis in kidney transplant patients with chronic hepatitis C virus infection: the TX-3 indexJOURNAL OF VIRAL HEPATITIS, Issue 6 2010L. L. Schiavon Summary., HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV-infected patients. This cross-sectional study included 102 KT individuals with positive HCV-RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR , F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX-3 model was 0.867 ± 0.081 (0.909, when adjusted by DANA). Values ,4.0 of TX-3 showed a NPV of 97% and scores >9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX-3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX-3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX-3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 ± 0.053 vs 0.762 ± 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV-infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients. [source] Monitoring SCCA-IgM complexes in serum predicts liver disease progression in patients with chronic hepatitisJOURNAL OF VIRAL HEPATITIS, Issue 4 2008A. Biasiolo Summary., About 30% of the patients with chronic hepatitis develop a progressive liver disease and one of the most intriguing issues is the detection of noninvasive markers for fibrosis stage and disease progression. High levels of squamous cell carcinoma antigen (SCCA)-immunoglobulin M (IgM) are detectable in hepatocellular carcinoma and their increase in cirrhotic patients can predict tumour development. As SCCA-IgM can also be detectable at low percentages in patients with chronic hepatitis, the aim of this study was to assess SCCA-IgM complexes in relation to disease outcome in this group of patients. An ELISA assay was used to determine the presence of SCCA-IgM in 188 patients with chronic hepatitis and in 100 controls. An additional serum sample was available after a median period of 6 years in 57 untreated patients: these patients were subdivided in group A, including eight patients with a fibrosis score increase ,2 in a second liver biopsy and group B, including 49 patients without fibrosis progression during a similar follow up. SCCA-IgM complexes were detectable in 63 of 188 (33%) patients but in none of the controls. A significant increase of SCCA-IgM levels over time was observed in patients with fibrosis progression (mean ± SD: 117 ± 200 U/mL/year), but not in those without histologic deterioration (mean ± SD: ,8.8 ± 31 U/mL/year, P < 0.0001). In conclusion, monitoring SCCA-IgM levels over time appears a useful approach to identify patients with chronic hepatitis at higher risk for cirrhosis development. [source] Noninvasive serum markers in the diagnosis of structural liver damage in chronic hepatitis C virus infectionLIVER INTERNATIONAL, Issue 9 2006Edison R. Parise Abstract: Aim: Several noninvasive markers are being used to assess the structural liver damage in patients with chronic hepatitis C (CHC). We evaluated the capacity of serum hyaluronic acid (HA), aspartate aminotransferase (AST)/ALT ratio, the AST to platelet ratio index (APRI) and ,-glutamyltransferase (GGT) levels to predict the intensity of hepatic fibrosis in patients with CHC. Patients and methods: In a total of 206 hepatitis C virus RNA-positive biopsied patients, AST, ALT, GGT levels, platelet count and serum HA concentration were determined. The APRI was calculated as the ratio of AST to platelets. Results: HA levels were best correlated with disease stage (r=,0.694; P<0.001). In the diagnosis of significant fibrosis (F2,F4), HA levels [AUC=0.879, 95% CI (0.832,0.927)] and APRI [AUC=0.824 (0.772,0.903)] were the markers with the best diagnostic accuracy. These parameters also best identified the presence of cirrhosis (F4), with an AUC of 0.908 (0.868,0.949) for HA and of 0.837 (0.772,0.903) for APRI. Conclusion: Serum HA was the parameter that alone presented the best diagnostic accuracy in the assessment of hepatic fibrosis in CHC. The APRI showed a better diagnostic sensitivity than GGT levels or the AST/ALT ratio. Its simple determination and low cost make this index a valid alternative for the noninvasive staging of CHC. [source] Markers of airway inflammation in primary ciliary dyskinesia studied using exhaled breath condensatePEDIATRIC PULMONOLOGY, Issue 6 2006MRCPCH, Nadwa Zihlif MD Abstract Macroscopically, the airways in primary ciliary dyskinesia (PCD) are inflamed and infected, and the eventual result is bronchiectasis. The measurement of noninvasive markers of inflammation in PCD may allow determination of mechanisms of tissue damage, and even allow monitoring of therapy. The aim of this study was to measure in exhaled breath condensate (EBC) of children with PCD the concentrations of the neutrophil chemoattractants leukotriene (LT) B4 and interleukin (IL)-8 and the marker of oxidative stress 8-isoprostane (8-IP), and to try determining whether these markers can be used to assess mechanisms of airway inflammation in these patients. Concentrations of LTB4, IL-8, and 8-IP in the EBC of 23 PCD and 11 age-matched healthy children were measured using an enzyme immunoassay (EIA). The children also performed spirometry and underwent sputum induction, the latter for differential cell count. The concentrations of 8-IP in EBC of children with stable PCD were significantly increased compared to normal controls (median, 7.8 pg/ml vs. 3.1 pg/ml; P,=,0.004). There was no difference in the median concentrations of EBC LTB4 between PCD subjects and healthy controls (28 pg/ml vs. 28 pg/ml; P,=,0.5). IL-8 levels were below the detection limit of the assay, and were not analyzed further. There was no correlation between concentrations of either 8-IP or LTB4 in EBC and forced expired volume in 1 sec in PCD children. Sputum induction was successful in 83% of the subjects; the median induced sputum neutrophil count was 69% (interquartile range, 59.3,73.6). No significant correlation was found between sputum neutrophils and either EBC 8-IP or LTB4 concentrations in PCD children. This study showed that oxidative stress, as reflected by increased exhaled 8-IP concentration, is increased in PCD children. The mechanism of airway neutrophilia is unclear, but is unlikely to be related to increased production of LTB4, at least in stable PCD patients. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source] Proteomic changes in rat serum, polymorphonuclear and mononuclear leukocytes after chronic nicotine administrationPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2005Chiara Piubelli Abstract In order to gain information about the effect triggered at the molecular level by nicotine, its neuroimmunomodulatory properties and its impact on the pathogenesis of inflammatory diseases, peripheral blood serum and leukocytes of rat submitted to passive nicotine administration were subjected to proteomic investigation. Serum, polymorphonuclear (PMN) and mononuclear (MN) leukocytes from chronically treated animals and from control animals were analysed by a two-dimensional (2-D) gel electrophoresis/mass spectrometry approach to detect differentially expressed proteins. The nicotine regimen selected is known to have a stimulatory effect on locomotor activity and to produce a sensitisation of the mesolimbic dopamine system mechanism involved in addiction development. After 2-D gel analysis and matching, 36,spots in serum, seven in PMN and five in MN were found to display a statistical difference in their expression and were subjected to matrix-assisted laser desorption/ionization-time of flight-mass spectrometry peptide fingerprinting for protein identification. Fifteen different proteins were identified. The results indicate an overall impact of nicotine on proteins involved in a variety of cellular and metabolic pathways, including acute phase response (suggesting the effect on inflammatory cascades and more in general on the immune system), oxidative stress metabolism and assembly and regulation of cytoskeleton. In particular, the observed changes imply a general reduction in the inflammatory response with a concomitant increased unbalance of the oxidative stress metabolism in the periphery and point to a number of potential noninvasive markers for the central nervous system (CNS) and non-CNS mediated activities of nicotine. [source] | ||||||||||||||||||||||