PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Biomarker variability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed2004

Metal-induced stress in bivalves living along a gradient of Cd contamination: relating sub-cellular metal distribution to population-level responses.

The use of biomarkers to assess the impacts of contaminants on aquatic ecosystems has noticeably increased over the past few years. Few of these studies, however, have contributed to the prediction of ecologically significant effects (i.e., at the population or community levels). The present field study was designed to evaluate the potential of metallothionein (MT) and sub-cellular metal partitioning measurements for predicting toxic effects at higher levels of the biological organization in freshwater bivalves (Pyganodon grandis) chronically exposed to Cd. For that purpose, we quantitatively sampled P. grandis populations in the littoral zone of nine lakes on the Precambrian Canadian Shield during two consecutive summers (1998 and 1999); lakes were characterized by contrasting Cd levels but similar trophic status. We tested relationships between the population status of P. grandis (i.e., growth parameters, density, biomass, secondary production, turnover ratio and cumulative fecundity) and (i) ambient Cd concentrations, (ii) sub-organismal responses (MT concentrations in the gill cytosol of individuals and Cd concentrations in three metal-ligand pools identified as M-HMW, the high molecular weight pool, M-MT, the metallothionein-like pool and M-LMW, the low molecular weight pool) and (iii) ecological confounding factors (food resources, presence of host fishes for the obligatory parasitic larval stage of P. grandis). Our results show that littoral density, live weight, dry viscera biomass, production and cumulative fecundity decreased with increasing concentrations of the free-cadmium ion in the environment (Pearson's r ranging from -0.63 to -0.78). On the other hand, theoretical maximum shell lengths (L( infinity )) in our populations were related to both the dissolved Ca concentration and food quality (sestonic C and N concentrations). Overall, Cd concentrations in the gill cytosolic HMW pool of the individual molluscs were the biomarker response that was most frequently and most strongly correlated with the population variables (Pearson's r ranging from -0.58 to -0.80). Our findings demonstrate, however, the difficulty of currently assigning to sub-cellular metal partitioning measurements (mainly Cd bound to the HMW fraction) any predictive role for population health, notably because of the influence of ecological confounding variables (e.g., the cumulative number of degree-days in the littoral zone, as is the case here). Metal contamination of our lakes has decreased markedly in the past 10 years and consequently we believe that the toxic effects of metals may have been replaced by some natural factors as the main agent for structuring the clam populations in these lakes.

Animals↗
PubMed2006

A descriptive study of variables associated with obtaining nipple aspirate fluid in a cohort of non-lactating women.

BACKGROUND: The search for biologic endpoints and biomarkers in the study of breast cancer risk assessment and risk reduction strategies has led to an interest in obtaining cytologic information and other biomarkers from nipple aspirate fluid (NAF). METHODS: This descriptive study examined factors associated with an increased ability to obtain NAF in a cohort of 3043 women between the ages of 15 and 89 years of age. The majority of women were between the ages of 30-49 (N = 1529/50.2%). Variables examined in relation to obtaining fluid include: age, marital status, age at menarche, menopausal status, a history of pregnancy, a history of breast-feeding, estrogen use, oral contraceptive use, endocrine disorders and tranquilizer use. RESULTS: On average, women from whom breast fluid was obtained were younger than women from whom breast fluid was attempted but not obtained (mean = 41.9 years versus 46.5 years, p < 0.0001). In unadjusted and age-adjusted comparisons, being married, a history of pregnancy, younger age at menarche (12 years of age or younger), tranquilizer use, oral contraceptive pill (OCP) use and endocrine problems were associated with an increased ability to obtain breast fluid. Post-menopausal status and exogenous estrogen use were associated with a decreased ability to obtain breast fluid. After age-adjustment, oral contraceptive use was no longer significantly associated with an increased ability to obtain fluid and post-menopausal status was no longer associated with a decreased ability to obtain breast fluid. After multivariate adjustment, age, being married, a history of pregnancy, tranquilizer use and a history of endocrine problems remained positively associated with the ability to obtain breast fluid. In addition, menopausal women who took estrogen were less likely to yield fluid than premenopausal women. CONCLUSION: Four variables (being married, history of pregnancy, tranquilizer use and endocrine disorders) remained positively associated with the ability to obtain NAF in all analyses. A younger age was consistently associated with a greater ability to obtain NAF in this and other studies.

Journal Article↗
PubMed2005

Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer.

BACKGROUND: Several studies looked for tumor biomarkers predictive for paclitaxel sensitivity but till now no reliable biomarkers are available. The aim of this study was to verify the potential predictive value of beta-tubulin III and IV, vascular endothelial growth factor-receptor (VEGFR-1), HER2/neu and microvessel density (mVD), in a group of 70 patients with advanced breast cancer (ABC) treated with paclitaxel-based chemotherapy. PATIENTS AND METHODS: Immunohistochemical analysis (ICA) of HER2, VEGFR-1, mVd, beta-tubulin III and beta-tubulin IV expression were performed in a series of 72 advanced breast cancer. Furthermore apoptotic fraction with TUNEL analysis was evaluated. RESULTS: beta-tubulin III ICA expression was predictive of progression after chemotherapy. In fact only 2% of the patients with low beta-tubulin III expression progressed after paclitaxel chemotherapy vs 38% of those with high beta-tubulin III tumor expression (P=0.000; by chi(2)). This evidence was confirmed by a logistic regression analysis (OR 28.789; 95% CI 3.212-258,072; P=0.004). There was not a significant association between other biomarkers' characteristics and clinical response to chemotherapy. A Cox multivariate analysis, with overall survival as a dependent variable, showed that only HER2 expression was independently associated (OR 2.39; 95% CI 1.09-5.23; P=0.03) with overall survival. CONCLUSIONS: We suggest that class III beta-tubulin immunohistochemical expression analysis could be a potentially relevant tumor biomarker for paclitaxel resistance in advanced breast cancer patients.

Adult↗
PubMed2004

Clinical significance of a single measurement of troponin-I and C-reactive protein at admission in 1773 consecutive patients with acute coronary syndromes.

BACKGROUND: The clinical significance of biochemical markers of myocardial damage or inflammation has not been prospectively established in populations representing the whole spectrum of acute coronary syndromes. We investigated whether the elevation of these biomarkers at admission has a prognostic value that is independent and incremental to baseline clinical variables and quantitative electrocardiographic ischemia. METHODS: We measured blood levels of cardiac troponin I (cTnI) and C-reactive protein (CRP) in 1773 consecutive patients admitted to 31 Italian coronary care units within 12 hours from an episode of acute coronary syndrome. Primary and secondary outcomes were (1) 30-day incidence of death or nonfatal (re)infarction and (2) death alone. RESULTS: In a multivariate model, cTnI was independently associated with the risk of death or (re)infarction (OR, 1.8; 95% CI, 1.2 to 2.6; P =.002) and death (OR, 2.2; 95% CI, 1.4 to 3.4; P <.001), whereas CRP was of borderline significance for the primary outcome but was associated with death (OR, 1.4; 95% CI, 1.0 to 2.1; P =.06, and OR, 1.7; 95% CI, 1.1 to 2.6; P =.01, respectively). However, the inclusion of the biomarkers did not increase the prognostic capacity of the clinical risk model (C-index of both models with and without biomarkers was 0.73 for the primary outcome measures and 0.80 for the secondary outcome measures). CRP further stratified cTnI-negative patients. The prognostic significance of the biomarkers was similar in patients with and in those without persistent ST-segment elevation. CONCLUSIONS: In acute coronary syndromes, the elevation of cTnI and CRP at admission has an independent prognostic value that is not incremental to baseline clinical variables and quantitative electrocardiographic ischemia.

Acute Disease↗
PubMed1988

Key questions in developing biomarkers of aging.

A series of questions is presented regarding a logical strategy for developing biomarkers of aging. The questions pertain to the conceptualization process in determining how to define aging and what extraneous and possibly confounding variables must be controlled in measuring this epiphenomenon. In addition, the investigator must consider the degree of generalization that is intended to apply to a candidate biomarker of aging. Empirical questions are also to be considered. Specifically, how will reliability and validity of the candidate biomarker be quantified and assessed? What statistical methods will be applied in this process? The need for biomarkers of aging as research tools in gerontology is argued, but the greater need for agreement on how to direct the conceptualization of this effort is also emphasized.

Aging↗
PubMed2005

Predictors of C-reactive protein in Tsimane' 2 to 15 year-olds in lowland Bolivia.

Infectious disease is a major global determinant of child morbidity and mortality, and energetic investment in immune defenses (even in the absence of overt disease) is an important life-history variable, with implications for human growth and development. This study uses a biomarker of immune activation (C-reactive protein) to investigate an important aspect of child health among the Tsimane', a relatively isolated Amerindian population in lowland Bolivia. Our objectives are twofold: 1) to describe the distribution of CRP by age and gender in a cross-sectional sample of 536 2-15-year-olds; and 2) to explore multiple measures of pathogen exposure, economic resources, and acculturation as predictors of increased CRP. The median blood-spot CRP concentration was 0.73 mg/l, with 12.9% of the sample having concentrations greater than 5 mg/L, indicating a relatively high degree of immune activation in this population. Age was the strongest predictor of CRP, with the highest concentrations found among younger individuals. Increased CRP was also associated with higher pathogen exposure, lower household economic resources, and increased maternal education and literacy. The measurement of CRP offers a direct, objective indicator of immune activation, and provides insights into a potentially important pathway through which environmental quality may shape child growth and health.

Acculturation↗
PubMed2005

Estimation of the Youden Index and its associated cutoff point.

The Youden Index is a frequently used summary measure of the ROC (Receiver Operating Characteristic) curve. It both, measures the effectiveness of a diagnostic marker and enables the selection of an optimal threshold value (cutoff point) for the marker. In this paper we compare several estimation procedures for the Youden Index and its associated cutoff point. These are based on (1) normal assumptions; (2) transformations to normality; (3) the empirical distribution function; (4) kernel smoothing. These are compared in terms of bias and root mean square error in a large variety of scenarios by means of an extensive simulation study. We find that the empirical method which is the most commonly used has the overall worst performance. In the estimation of the Youden Index the kernel is generally the best unless the data can be well transformed to achieve normality whereas in estimation of the optimal threshold value results are more variable.

Algorithms↗
PubMed2006

Proteomic analysis in cancer research: potential application in clinical use.

The ultimate goal of cancer proteomics is to adapt proteomic technologies for routine use in clinical laboratories for the purpose of diagnostic and prognostic classification of disease states, as well as in evaluating drug toxicity and efficacy. The novel technologies allows researchers to facilitate the comprehensive analyses of genomes, transcriptomes, and proteomes in health and disease. The information that is expected from such technologies may soon exert a dramatic change in cancer research and impact dramatically on the care of cancer patients. Analysis of tumor-specific proteomic profiles may also allow better understanding of tumor development and the identification of novel targets for cancer therapy. The localization of gene products, which is often difficult to deduce from the sequence, can be determined experimentally. Mechanisms, such as regulation of protein function by proteolysis, recycling, and isolation in cell compartments, affect gene products, not genes. Finally, protein-protein interactions and the molecular composition of cellular structures can be determined only at the protein level. The biological variability among patient samples as well as the great dynamic range of biomarker concentrations are currently the main challenges facing efforts to deduce diagnostic patterns that are unique to specific disease states. While several strategies exist to address this problem, we have tried to offer a wide perspective about the current possibilities.

Antibodies, Neoplasm↗
PubMed2006

Long-term heart rate variability as a predictor of patient age.

Patients age has been estimated in healthy population by means of the heart rate variability (HRV) parameters to assess the potentiality of HRV indexes as a biomarker of age. A long-term analysis of HRV has been performed, computing linear time and frequency domain parameters as well as non-linear metrics, in a dataset of 113 healthy subjects (age range 20-85 years old). The principal component analysis has been used to capture age-related influence on HRV and then three different models have been applied to predict subjects age: a robust linear regressor (RLR), a feedforward neural network (FFNN) and a radial basis function neural network (RBFNN). A good prediction of patient age has been obtained (using all principal components, the Pearson correlation coefficient between predicted and real age: RLR=0.793; FFNN=0.872; RBFNN=0.829), even if an overestimation in younger subjects and an underestimation in older ones may be observed. The important and complementary contribution of non-linear indexes to aging related HRV modifications has also been underlined.

Adult↗
PubMed2004

Hormones and mammographic breast density.

Mammographic density reveals information about the hormonal environment along with the heritability in which breast cancer develops. This is made possible by the widespread use of population screening by mammography. Increasingly this is an important observation not just for population studies, which reveal disease determinants, but also for the individual. Density reveals the effect of the intrinsic hormonal environment and its background genetics, and also the effect of pharmaceuticals--agents used for disease control and prevention and hormone replacement therapy (HRT) used for well-being around the menopause. Increasingly this focus on the individual will need methods of measurement of density that can be monitored with greater accuracy than the widely used BI-RADS 4 categories. For this purpose studies are under way to measure volume of dense tissue as a continuous variable. In due course, measurement of density will be used as a biomarker of risk, employed in risk models and to monitor interventions. Before this can happen more knowledge will be needed of the change occurring naturally through the menopause and the differences between individuals. This will need specific study backed up with detailed information about the patient on large numbers of women and their mammograms. Currently the widespread use of HRT has increased the prevalence of the dense patterns and potentially may adversely affect the effectiveness of mammographic screening programmes. There is a large literature recording this from which we see that combined continuous preparations of oestrogen progestin are more likely to cause increased density than oestrogen alone or tibolone. Breast density, measured more accurately, has the potential to be an important adjunct to risk estimation and to monitor interventions for breast cancer prevention with pharmaceuticals (such as SERMS) and by change in lifestyle behaviours.

Breast↗
PubMed2001

Are high density lipoprotein (HDL) and triglyceride levels relevant in stroke prevention?

Although statins reduce the risk of non-haemorrhagic strokes and transient ischaemic attacks (TIA), little is known about the efficacy of fibrates. This situation has been partly remedied by the recent publication of two-fibrate based trials--The Veterans Affairs High Density Lipoprotein Cholesterol Intervention Trial (VAHIT) and the Bezafibrate Infarction Prevention Trial (BIP). In BIP, bezafibrate did not significantly reduce the risk of a cerebrovascular event (CVE). Bezafibrate increased the high density lipoprotein cholesterol (HDL) level by 18% to 40 mg/dl (1.03 mmol/l) and decreased triglyceride (TG) levels by 21% to 115 mg/dl (1.29 mmol/l). In contrast, in VAHIT, gemfibrozil significantly reduced the risk of investigators designated stroke (P=0.04) and TIA (P<0.001). Gemfibrozil increased HDL by 6% to 33 mg/dl (0.85 mmol/l) and decreased TG by 31% to 110 mg/dl (1.25 mmol/l). However, the baseline low density lipoprotein cholesterol (LDL) levels were higher in BIP than in VAHIT (148 versus 111 mg/dl; 3.82 versus 2.87 mmol/l). LDL levels were not markedly altered by treatment in either trial. Fibrates can improve several CVE predictors, like fibrinogen, lipoprotein (a), insulin sensitivity and platelet activity. Furthermore, lowered HDL and/or raised TG levels are associated with an increased risk of a CVE; fibrates are an appropriate treatment for this lipid profile. In conclusion, the evidence suggests that not only total cholesterol and LDL, but also HDL and TG levels predict the risk of a CVE. Statins, fibrates or a combination of these drugs can modify these variables.

Adult↗
PubMed2026

A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.

INTRODUCTION: Cancer cell proliferation occurs within the context of persistent genomic instability. In this review, we propose the RS-CCD-CIN axis as a systems-level framework in which replication stress (RS), cell cycle deregulation (CCD) and chromosomal instability (CIN) form an interdependent triad that shapes tumour evolution. This axis represents a constrained metastable state in which genomic instability is tolerated and buffered. The objective of this review is to synthesize the current understanding of how the RS-CCD-CIN axis contributes to tumour heterogeneity, adaptability and therapy response. DISCUSSION: Evidence indicates that RS, CCD and CIN operate as a dynamic, interconnected network rather than as independent processes. Replication stress induces DNA damage and mutagenesis, while partial checkpoint disruption permits cells with unresolved lesions to proliferate. Chromosomal instability generates both structural and numerical alterations, contributing to intratumoural heterogeneity. Together, these processes facilitate adaptation to environmental and therapeutic pressures. Extrachromosomal DNA, micronuclei formation and cytosolic DNA signalling, including the cGAS-STING pathway, connect genomic instability to adaptive responses and immune modulation. Single-cell and spatial profiling reveal temporal and spatial variability in RS, CCD and CIN states, highlighting the limitations of static biomarkers. Therapeutically, targeting individual components often yields limited durability, whereas approaches that simultaneously perturb multiple aspects of the RS-CCD-CIN axis may improve clinical outcomes. CONCLUSIONS: This review highlights the RS-CCD-CIN axis as a fragile and metastable architecture that supports cancer evolution, while also being susceptible to collapse. A deeper understanding of this interconnected framework may inform the development of therapeutic strategies and enhance the management of resistance.

Humans↗
PubMed2003

The safety testing of amino acids.

The risk assessment of compounds added to foods or taken as supplements is usually based on hazard characterization studies performed in animal test species. A large default uncertainty factor, or margin or exposure, is usually required to allow for possible species differences and human variability in the toxicokinetics and toxicodynamics of the compound. The development of biomarkers offers the potential to rationalize the risk assessment of amino acids, and to refine the extrapolation of data from animals to humans. The use of high resolution nuclear magnetic resonance spectroscopy applied to readily accessible biological fluids, such as urine and plasma, offers great potential for the identification of toxicologically relevant biomarkers in animal studies that can then be applied to studies in humans.

Amino Acids↗
PubMed1998

Single cell gel electrophoresis assay: sensitivity of peripheral white blood cells in human population studies.

The single cell gel electrophoresis assay (Comet assay) was selected as a biomarker of exposure to evaluate the impact of air pollution and lifestyle variables on hospitalized pregnancies in two districts with different air pollution levels in northern (Teplice) and southern (Prachatice) Bohemia. The hypothesis was that the DNA damage detected as single strand breaks would be generally higher in the district with higher air pollution levels. To undertake the study we enrolled 322 pregnancies in Teplice and 220 in Prachatice. Venous and cord blood were analysed using the original alkaline Comet assay procedure with lysis for 60 min, unwinding for 40 min and electrophoresis for 24 min. We also used a modified procedure in which unwinding was prolonged to 60 min and electrophoresis to 40 min. Peripheral white blood cells (WBC) were analysed using an image analyser system. When we analysed the results obtained for mothers and their children no differences were found between polluted and control districts. The prolongation of alkali unwinding and electrophoresis did not increase sensitivity of the assay. No effects of prematurity, ethnicity, smoking or GSTM1 polymorphism were observed for any of the Comet parameters. Multiple regression analyses were performed for the European population (n = 285). A statistical model was fitted to determine the relationship between the Comet parameters of mothers and their children. According to our results it seems that the Comet assay was not a particularly sensitive technique to determine the effects of environmental pollution at the DNA level if peripheral WBC are used.

Air Pollutants↗
PubMed2001

Interrelations of lead levels in bone, venous blood, and umbilical cord blood with exogenous lead exposure through maternal plasma lead in peripartum women.

Recent research has raised the possibility that fetal lead exposure is not estimated adequately by measuring lead content in maternal whole blood lead because of the variable partitioning of lead in whole blood between plasma and red blood cells. Lead in maternal plasma may derive in large part from maternal bone lead stores. In this study we aimed to estimate the contribution of maternal whole blood lead, maternal bone lead levels, and environmental lead to umbilical cord blood lead levels (as a measure of fetal lead exposure). In the model, we assumed that lead from all of these sources reaches the fetus through the maternal plasma lead pathway. In 1994-1995, we recruited 615 pregnant women for a study of lead exposure and reproductive outcomes in Mexico City. We gathered maternal and umbilical cord blood samples within 12 hr of each infant's delivery and measured maternal lead levels in cortical bone and trabecular bone by a K-X-ray fluorescence (K-XRF) instrument within 1 month after delivery. We administered a questionnaire to assess use of lead-glazed ceramics (LGC) to cook food and we obtained data on regional air lead levels during the 2 months before delivery. We used structural equation models (SEMs) to estimate plasma lead as the unmeasured (latent) variable and to quantify the interrelations of plasma lead, the other lead biomarkers, and environmental lead exposure. In the SEM analysis, a model that allowed plasma lead to vary freely from whole blood lead explained the variance of cord blood lead (as reflected by a total model R(2); R(2) = 0.79) better than did a model without plasma lead (r(2) = 0.67). Cortical bone lead, trabecular bone lead, use of LGC, and mean air lead level contributed significantly to plasma lead. The exchange of lead between plasma and red blood cells was mostly in the direction of plasma to cells. According to the final model, an increase in trabecular bone lead and cortical bone lead was associated with increases in cord blood lead of 0.65 and 0.25 microg/dL, respectively. An increase of 0.1 microg/m(3) in air lead was associated with an increase in the mean level of fetal cord blood lead by 0.67 microg/dL. With one additional day of LCG use per week in the peripartum period, the mean fetal blood lead level increased by 0.27 microg/dL. Our analyses suggested that maternal plasma lead varies independently from maternal whole blood lead and that the greatest influences on maternal plasma lead are maternal bone lead stores, air lead exposures, and recent cooking with LGC. The contributions from endogenous (bone) and exogenous (environmental) sources were relatively equal. Measurement of plasma and bone lead may be important in accurately assessing fetal lead exposure and its major sources, particularly if exogenous exposures decline.

Air Pollutants↗
PubMed1995

Air toxics and asthma: impacts and end points.

The National Urban Air Toxics Research Center (NUATRC) hosted a medical/scientific workshop focused on possible asthma/air toxics relationships, with the results of the NUATRC's first research contract with the University of Cincinnati as the point of discussion. The workshop was held at the Texas Medical Center on 4 February 1994 and featured presentations by distinguished academic, government, and industry scientists. This one-day session explored the impact of various environmental factors, including air toxics, on asthma incidence and exacerbation; an emphasis was placed on future research directions to be pursued in the asthma/air toxics area. A key research presentation on the association of air toxics and asthma, based on the study sponsored by NUATRC, was given by Dr. George Leikauf of the University of Cincinnati Medical Center. Additional presentations were made by H. A. Boushey, Jr., Cardiovascular Research Institute/University of California at San Francisco, who spoke on of the Basic Mechanisms of Asthma; K. Sexton, U.S. Environmental Protection Agency, who spoke on hazardous air pollutants: science/policy interface; and D. V. Bates, Department of Health Care and Epidemiology at the University of British Columbia, who spoke on asthma epidemiology. H. Koren, U.S. Environmental Protection Agency, and M. Yeung, of the Respiratory Division/University of British Columbia, Vancouver General Hospital, discussed occupational health impacts on asthma. Doyle Pendleton, Texas Natural Resource Conservation Commission, reviewed air quality measurements in Texas. The information presented at the workshop suggested a possible association of asthma exacerbations with ozone and particulate matter (PM10); however, direct relationships between worsening asthma and air toxic ambient levels were not established. Possible respiratory health effects associated with air toxics will require considerably more investigation, especially in the area of human exposure assessment. Two major recommendations for future research resulted from this workshop and an accompanying NUATRC Scientific Advisory Panel meeting: a need for more complete individual personal exposure assessments so that accurate determinations of actual personal exposures to various pollutants can be made; and a need for field experiments utilizing biomarkers of exposure and effect to more accurately assess the extent and variability of the biological effects, if any, of individual air toxics.

Air Pollutants↗