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Results for “Biomarker variability”

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PubMed2005

Urinary metal and polycyclic aromatic hydrocarbon biomarkers in boilermakers exposed to metal fume and residual oil fly ash.

BACKGROUND: Boilermakers are occupationally exposed to known carcinogens. METHODS: The association of urinary 1-hydroxy-pyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbon (PAH) exposure, with biomarkers of metal exposure (vanadium, chromium, manganese, nickel, copper, and lead) in boilermakers exposed to metal fume from welding and dust particulates from residual oil fly ash (ROFA) was examined. A repeated measures cohort study was conducted during the overhaul of an oil-fired boiler. Twice-daily urine samples were obtained for 5 days and analyzed for cotinine, 1-OHP, and metals. Generalized estimating equations (GEE) were used to model the multivariate relationship of 1-OHP to the explanatory variables. RESULTS: Metal and 1-OHP levels were determined for 165 urine samples from 20 boilermakers and these levels increased during the workweek. However, the 1-OHP level was not significantly associated with any individual metal level at any time point. CONCLUSION: This suggests that boilermakers were occupationally exposed to PAH and metals, but 1-OHP as a PAH biomarker was unable to serve as a surrogate marker of metal exposure for the metals measured in this study.

Adolescent↗

PubMed2002

Trichloroacetic acid as a biomarker of exposure to disinfection by-products in drinking water: a human exposure trial in Adelaide, Australia.

We addressed the need for a biomarker of ingestion exposure to drinking water disinfection by-products by performing a human exposure trial. We evaluated urinary excretion of trichloroacetic acid (TCAA) as an exposure biomarker using 10 volunteers who normally consume their domestic tap water. We recruited the volunteers at a water quality research laboratory in Adelaide, Australia. Participants maintained a detailed consumption and exposure diary over the 5-week study. We also analyzed tap water and first morning urine (FMU) samples for TCAA, and tap water for chloral hydrate (CH). We documented both interindividual and intraindividual variability in TCAA ingestion and urinary excretion, and both were substantial. With a TCAA-free bottled water intervention, we used creatinine-adjusted urinary TCAA levels to estimate urinary TCAA excretion half-lives for three of the participants. We observed correspondence over time between estimated TCAA excretion, calculated from TCAA + CH ingestion levels, and measured TCAA urinary excretion. This study demonstrates the merits and feasibility of using TCAA in FMU as an exposure biomarker, and reveals remaining concerns about possible alternate sources of TCAA exposure for individuals with low drinking water ingestion exposure.

Adult↗

PubMed2000

Relationship between histological prognosis of chronic hepatitis C and amount of hepatitis C virus core protein in serum.

BACKGROUND: Hepatitis C virus (HCV) viraemia is one of the factors for histological prognosis of chronic hepatitis C. METHODS: One hundred and thirty-five patients who received hepatic biopsies twice at intervals of 5 years or longer were followed up for a mean of 9.7 +/- 4.0 years were studied retrospectively. The amount of HCV viraemia present was measured as the concentration of HCV core protein by using the fluorescence enzyme immunoassay method. RESULTS: Multiple-regression analysis, using deterioration of the histological stage as a dependent variable, showed that greater age (P = 0.041), higher stage of hepatic histology at the start of follow up (P = 0.029), and higher serum concentration of core protein (P < 0.001) were independent factors affecting the deterioration of the liver's histological stage. At follow up, no significant difference in histological stage was seen between patients with serum HCV core protein > or = 100 pg/mL (n = 60) and those with serum core protein < 100 pg/mL (n = 75). The histological grade in patients with high serum core-protein levels tended to be significantly worse and the deterioration rate of the histological stage was significantly higher than in those with low HCV core protein levels (68 vs 35%, P < 0.001). The mutation rate of the HCV envelope-2/non-structural 1 (E2/NS1) nucleotide region was compared in two patients who had high serum concentrations of HCV core protein and whose histological stage had deteriorated with two patients who had low serum concentrations of the core protein and whose histological stages remained unchanged. No significant difference in E2/NS1 mutation was found. CONCLUSIONS: The amount of HCV viraemia was suggested to be a significant factor for determining histological outcome in patients with chronic hepatitis C. The mutation rate in the E2/NS1 region did not seem to be associated with the prognosis of chronic hepatitis C.

Adult↗

PubMed2005

Metallothioneins in aquatic invertebrates: their role in metal detoxification and their use as biomarkers.

The literature on metallothioneins (MT) and metallothionein-like proteins (MTLP) in aquatic invertebrates is large and increasing, and yet inconsistencies and confusion remain, not least over the physiological role of MT and their use as biomarkers in environmental monitoring programmes. We have collated published information on MT in three important groups of aquatic invertebrates-the molluscs, crustaceans and annelid worms, and attempted to seek explanations for some of the apparent inconsistencies present in the dataset. MTs can be induced by the essential metals Cu and Zn and the non-essential metals Cd, Ag and Hg in both vertebrates and invertebrates, but their induction is variable. Such variation is intraspecific and interspecific, and is down to a variety of reasons environmental and physiological explored here. Against this background of variability MTs do appear to play roles both in the routine metabolic handling of essential Cu and Zn, but also in the detoxification of excess amounts intracellularly of these metals and of non-essential Cd, Ag and Hg. Different isoforms of MT probably play different physiological roles, and the dependence on MT in detoxification processes varies environmentally and between zoological groups. MTs can be used as biomarkers if used wisely in well-designed environmental monitoring programmes.

Animal Structures↗

PubMedDate not supplied

Male breast cancer.

Male breast cancer is an uncommon malignancy, making it difficult to accurately define the features and optimal management of this disease. As more information is generated, it appears that the pathogenesis is related in large part to hormonal alterations but that the histologic features, biologic behavior, and prognosis are similar to tumors in female patients. As a result of larger studies based upon female patients, treatment algorithms have evolved to include multimodality therapy and less radical surgery. Continued research of this disease will continue to define improved methods of detection, prevention, and treatment, and, without the confounding variables of the menstrual cycle, menopause, and childbirth, may also provide a clearer understanding of breast cancer in women.

Algorithms↗

PubMed2004

Total cell-free DNA (beta-globin gene) distribution in maternal plasma at the second trimester: a new prospective for preeclampsia screening.

OBJECTIVES: Levels of cell-free foetal DNA (f-DNA) in maternal plasma are higher in those asymptomatic subjects who will eventually develop preeclampsia. f-DNA is, however, informative only for those women bearing a male foetus, by amplification of Y-specific sequences and represents a small fraction of total circulating DNA that can be dosed by using ubiquitous genes as well as beta-globin. In this study, we examined the quantitative distribution of total DNA by amplification of beta-globin gene, in asymptomatic women matched with controls to evaluate its possible role in predicting preeclampsia. METHODS: Forty-eight low-risk women (8 asymptomatic cases matched for gestational age at the second trimester with 40 controls) were enrolled in the present study. beta-globin concentrations were converted into multiples of the median of the controls (MoM), in order to assess the possible different distribution of beta-globin MoM in cases and controls. RESULTS: MoM values were as follows: controls, 1.00 +/- 0.59; asymptomatic cases, 1.99 +/- 1.95. After Gaussian conversion of data, at a false-positive rate (FPR) of 5%, the detection rate (DR) was 46%. CONCLUSION: beta-globin (total DNA) levels are higher in those patients who subsequently developed preeclampsia and can potentially be used in screening for early detection of the disease. These findings represent a step forward in the study of cell-free DNA in maternal blood as a screening variable, because it overcomes the gender limitations of foetal DNA screening.

Biomarkers↗

PubMed2005

[Significance of the PSA-concentration for the detection of prostate cancer].

Prostate cancer among adult males is the most common neoplasm in western countries. Prostate specific antigen (PSA) is now a well established tumor marker that aids in the early detection of localized prostate cancer. Increased PSA concentrations are found in the serum of patients with benign prostatic hyperplasia or patients with prostate cancer, respectively. Therefore, in general the specificity of this test is low. The diagnostic value of PSA can be improved in consideration of clinical data, patients age, the measurement of free or complexed PSA, and the measurement of PSA velocity, respectively. Furthermore, there is a high variability between commercial PSA assays. Finally, the pre-analytical laboratory procedures have a high impact on the PSA measurement.

Aged↗

PubMed2005

Comparison of serum lipid values in patients with coronary artery disease at <50, 50 to 59, 60 to 69, and >70 years of age.

We evaluated the relation between lipids and precocity of coronary artery disease (CAD) in the real world as characterized by increasing statin use. The highest mean values of total cholesterol, low-density lipoprotein cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and ratio of triglycerides to HDL cholesterol were found when CAD was detected in patients who were <50 years of age (p <0.01 for all); the opposite occurred for HDL cholesterol (p <0.01). Triglycerides and ratio of triglycerides to HDL cholesterol were the most powerful, independent variables related to precocity of CAD.

Adult↗

PubMed2006

Less than 50% of variation in HDL cholesterol between and within individuals, is explained by established predictors.

Variation in serum high density lipoprotein cholesterol (HDL-C) concentrations is believed to be largely explained by triglycerides, but this has been mainly explored in cross-sectional analyses. Eight hundred and eighty one white male participants in a health screening program attended on a total of 2158 occasions for measurements that included fasting HDL-C, low density lipoprotein cholesterol (LDL-C) and homeostasis model assessment insulin resistance (HOMA-R). Baseline, change between-visit and repeated-measures regression models were used to analyse predictors of between- and within-individual variation in HDL-C. Independent predictors of between-individual variation included serum triglycerides (20.3 or 19.6% of the variance explained, depending on the model used), body mass index (BMI: 4.7 and 4.3%), cigarette smoking (3.3 and 1.5%) and alcohol consumption (0.4 and 1.1%). Within-individual variation in HDL-C was explained by changes in serum triglycerides (4.7 and 7.5%) and BMI (5.3 and 2.9%). In multivariate models, 24.3 and 24.9% of between-individual variation in HDL-C, and 7.9 and 8.8% of within-individual variation could be explained, depending on the model used. Sixty percent of the variation in HDL-C was due to unobserved factors. The majority of variation in HDL-C remains to be explained by influences other than the conventional variables: triglyceride and LDL cholesterol concentrations, insulin resistance, smoking and alcohol.

Alcohol Drinking↗

PubMed1991

Effects of alcohol intake on plasma fatty acids assessed independently of diet and smoking habits.

1. This study was designed to determine prospectively whether changing alcohol consumption influenced the proportion of plasma linoleic acid independently of diet or smoking habits, and to evaluate changes in the plasma linoleic acid concentration as a potential marker of changes in alcohol consumption. 2. Fasting plasma fatty acid profiles were investigated in 72 male drinkers who were randomly assigned to drink low-alcohol beer or to maintain their usual drinking habits for a period of 4 weeks. 3. At entry to the study, a higher alcohol intake was associated with lower proportions of plasma linoleic acid, arachidonic acid and dihomolinolenic acid and higher proportions of plasma palmitoleic acid, independently of changes in body mass index. Smoking habits were unchanged and there were no major changes in diet during the period of the intervention. 4. Because the plasma palmitoleic acid concentration has been suggested as a possible marker of 'at risk' drinking, we investigated plasma fatty acid concentrations as indicators of alcohol intake. The plasma palmitoleic acid concentration was not a useful discriminator. Indices determined using logistic regression and combining plasma apolipoprotein A-II and linoleic acid concentrations gave better discrimination than either variable alone.

Adult↗

PubMed2001

p27 immunostaining is related to prognosis in malignant mesothelioma.

AIMS: To evaluate the prognostic value of the proliferation-associated antigen p27 in malignant mesothelioma. METHODS AND RESULTS: Sections from 36 patients with malignant mesothelioma were immunohistochemically stained for the p27 antigen. The results were quantified by recording the proportion of positively stained nuclei and these data were tested for association with patient survival. p27 expression was also compared with tumour type, MIB-1 expression, apoptotic and mitotic indices. Patients with pleural malignant mesothelioma showing low p27 expression (< 53% of cells positive) survived for significantly shorter periods of time than those with high p27 expression (> or = 53% of cells positive) (P=0.04). The 50% survival time of subjects with low p27 was 4-6 months whereas for those with high p27 expression it was 10-11 months. There was no significant association between p27 expression and MIB-1, apoptotic or mitotic indices. CONCLUSIONS: Low p27 expression in pleural malignant mesothelioma is associated with a significantly worse prognosis. p27 appears to be an independent prognostic variable which may be of value in counselling patients with malignant mesothelioma.

Antigens, Nuclear↗

PubMed2002

Seroprevalence of hepatitis C markers among intravenous drug users in western European countries: a systematic review.

Currently, the most important risk factor for hepatitis C virus (HCV) infection in Europe is intravenous drug use. To establish a better insight into the epidemiology of hepatitis C among intravenous drug users (IVDUs) in western European countries a systematic review on the prevalence of hepatitis C markers and their determinants was performed. Reports were identified by searches on Medline and on the internet and by screening reference lists of selected papers. The prevalence rates of anti-HCV in western European IVDUs reported in the 66 studies selected for analysis, ranged between 37 and 98%. No relation was found between prevalence rates and mean age, mean duration of intravenous drug use, geographical area, setting of the study, method of recruitment or the year(s) of collection of samples. Eleven studies concerning the prevalence of HCV-RNA in hepatitis C-infected IVDUs were selected for analysis. Prevalence rates ranged from 26 to 86%. Based on five studies, a statistically significant positive linear relation was found between the mean age of study population and the prevalence of HCV-RNA. Our analysis revealed considerable variation in prevalence rates of hepatitis C markers among IVDUs in western Europe. We found no conclusive explanation for this variability. Further research investigating the dynamics of the hepatitis C epidemic in IVDUs is necessary.

Adult↗

PubMed2001

Assessment of nutritional status using biochemical and anthropometric variables in a nutritional intervention study of women with hip fracture.

BACKGROUND & AIMS: The aim of this study of women with hip fracture was to describe nutritional status with biochemical markers and anthropometric variables, and to evaluate the effect of nutritional intervention with the intention of increasing protein and energy intake. METHODS: The first consecutive 44 women were included, and used as controls. The next 44 were matched for age, fracture and mental state. Anthropometric variables, IGF-I, hormones and serum albumin were collected 4--6 days (baseline), 1 and 3 months after surgery. Twenty-four women filled out a 7-day food record. RESULTS: At baseline, one fourth had BMI <20 kg/m(2)and subnormal triceps skinfold thickness. Baseline serum albumin, IGF-I and growth hormone levels were low, probably as an acute response to trauma. Women with BMI <20 kg/m(2)had lower IGF-I levels compared to those with higher BMI. At 3 months, one-third of both groups were protein and energy malnourished. The intervention group obtained higher daily energy percentage from fat but none of the groups reached their calculated energy need. CONCLUSIONS: Using biochemical markers in the acute postoperative situation to assess nutritional status is not recommended. The intervention had no impact on anthropometric or biochemical variables.

Activities of Daily Living↗

PubMed2006

Prognostic factors in non-metastatic Ewing's sarcoma tumor of bone: an analysis of 579 patients treated at a single institution with adjuvant or neoadjuvant chemotherapy between 1972 and 1998.

We aimed to identify pretreatment and treatment factors that may influence the outcome of Ewing's sarcoma family tumors of bone and enable customized therapy for future studies with a retrospective analysis of 579 patients with non-metastatic Ewing's sarcoma treated with combined adjuvant or neoadjuvant chemotherapy at a single institution between 1972 and 1998. We evaluated the prognostic significance of gender, age, site and volume of tumor, serum level of LDH, type of local treatment, type of chemotherapy and histologic response to preoperative treatment. The 5- and 10-year disease-free survival rates were 56.9% and 49.2% respectively. Multivariate analyses showed that all the evaluated factors, with exclusion of the tumor site, were significantly correlated with the 5-year disease-free survival. We concluded that the outcome of non-metastatic ESF of bone tumors is influenced by many clinical and treatment-correlated variables. In order to gain the greatest benefit from treatment, while reducing the morbidity, appropriate therapeutic strategies for different risk groups of patients should be selected. Criteria to stratify patients according to the risk of local or systemic relapse should not be based on a single prognostic factor, but should include all the variables that showed prognostic significance.

Adolescent↗

PubMed1989

Circulating T-lymphocyte sub-subsets and NK-like cells in renal transplant patients: patterns associated with rejection.

The patterns of circulating T sub-subset and NK-like cells were monitored in 87 renal transplant patients on a total of 122 occasions. Combinations of monoclonal antibodies were used in two-colour flow cytometric (FACS) analysis to define the major T helper/inducer and T suppressor/cytotoxic subsets and their activated counterparts, the T suppressor inducer and T suppressor effector sub-subsets, NK-like cells and their activated counterparts. In patients with rejection, the proportions of T suppressor inducer and T suppressor effector cells were less and the proportion of activated NK-like cells greater compared with cases exhibiting stable graft function, and these group differences were highly significant. Analysis with stepwise multivariate logistic regression showed that combinations of several functional/activated lymphocyte subsets allow a predictive diagnostic power which is superior to the use of single variables.

Antibodies, Monoclonal↗

PubMed2003

Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura.

Several immunohistochemical markers, among them calretinin, thrombomodulin (CD141), keratin 5, and mesothelin, have been documented or suggested as useful markers for positive identification of mesothelioma and to differentiate it from pulmonary adenocarcinoma; numerous studies have documented their variable specificity. However, expression of these markers in other types of lung carcinomas has not been systematically explored, although these tumors can enter in the differential diagnosis of mesothelioma. In this study we immunohistochemically evaluated 596 lung carcinomas of different types for the four above-mentioned mesothelioma markers, all of which reacted with a great majority of epithelioid mesotheliomas studied for comparison. Calretinin expression was common in giant cell carcinomas (67%), small cell carcinomas (49%), and large cell carcinomas (38%), whereas it was rare in usual adenocarcinomas but slightly more common in those with neuroendocrine differentiation (11% and 17%, respectively). Thrombomodulin was present in all keratinizing squamous carcinomas and the great majority (87%) of nonkeratinizing tumors in a membrane-staining pattern. It was moderately common in small cell (27%) and large cell carcinomas (25%) but relatively rare in adenocarcinomas (13%). Keratin 5 was expressed in all keratinizing and the great majority (87%) of nonkeratinizing squamous carcinomas, and a majority of large cell carcinomas (56%) and some small cell carcinomas (27%). It was rare in acinar adenocarcinomas (12%) and absent in those with neuroendocrine differentiation. Mesothelin was present in more than half (53%) of adenocarcinomas and a minority (13%) of large cell carcinomas but was absent in small cell carcinomas. In squamous carcinomas it was more often seen in nonkeratinizing versus keratinizing tumors (31% vs 16%). These results show that each of these "mesothelioma" markers reacts with different subsets of pulmonary carcinomas with a variable frequency; this should be considered when using these markers in the differential diagnosis of thoracic tumors.

Biomarkers, Tumor↗

PubMed1997

Markers of risk after acute myocardial infarction. A comparison of clinical variables, ambulatory and exercise electrocardiography, echocardiography, and stress echocardiography.

BACKGROUND: Short-term mortality after myocardial infarction has decreased continuously among members of selected populations. Nonetheless, the long-term prognosis among members of unselected populations remains bad. Further research in risk stratification is therefore needed. In the present study we tested the additive value of clinical variables, echocadiography, ambulatory electrocardiography, exercise testing, and stress echocardiography in assessing the long-term prognosis after acute myocardial infarction. METHODS: Two-dimensional echocardiography and ambulatory electrocardiography (analysis of ST-segment changes and of heart rate variability) were performed for 74 patients aged < 75 years who had had an acute myocardial infarction. Before their discharge from hospital, 70 patients were subjected to a combined exercise test and stress echocardiography. The time of follow-up was > or = 3 years. RESULTS: During follow-up 18 patients died, and 38 suffered cardiac events defined as death, nonfatal reinfarction and the need for revascularization. We first tested 31 covariates in a univariate regression analysis. A subsequent multivariate analysis was performed in two stages. During the first of these, clinical variables (a history of systemic hypertension, infarct localization, and diabetes mellitus) and variables derived from noninvasive tests (new-onset wall-motion abnormality during stress echocardiography, ST-segment depression and heart-rate variability during ambulatory electrocardiography, the ejection fraction by echocardiography at rest, and the double product during exercise tests) predicted mortality. After the second stage, however, the only remaining independent predictors of mortality were the presence of a new-onset wall-motion abnormality (P < 0.0001, relative risk 13.5, 95% confidence interval 3.6-51.3), ST-segment depression during ambulatory electrocardiography (P = 0.003, relative risk 5.0, 95% confidence interval 1.7-15.7) and a decreased heart rate variability (P = 0.007). CONCLUSIONS: The only variables that were of independent value in assessing the long-term mortality were those expressing residual myocardial ischemia and the cardiovascular sympatho-vagal balance. It is, therefore, recommended that one should monitor these variables for patients recovering from an acute myocardial infarction.

Aged↗

PubMed2006

Unexpected smoking-linked high MMP-9 in induced sputum of hazardous dust-exposed workers.

We investigated whether metalloproteinase-9 (MMP-9) values in induced sputum (IS) and pulmonary function tests can serve as a marker of damage and intensity of exposure to hazardous dust. Thirty-nine factory employees (28 workers exposed to metal particles and 11 supposedly nonexposed office workers) underwent IS induction. Samples were processed by conventional methods within 2 hours. The proportion of particles with diameters of 0-2 mu in IS samples was significantly higher in nonexposed than exposed workers and in smoker compared to nonsmoker workers. MMP-9 and TIMP-1 levels were similar for both groups. A linear regression model for MMP-9 based on exposure, smoking habits, and proportion of particles < 5 mu revealed a positive correlation between each of the explanatory variables and MMP-9 values. MMP-9 may serve as a marker for pulmonary injury.

Adult↗