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Results for “Biomarker variability”

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PubMed2003

Bivariate longitudinal model for the analysis of the evolution of HIV RNA and CD4 cell count in HIV infection taking into account left censoring of HIV RNA measures.

We present a bivariate linear mixed model taking into account censored measures of the response variable due to lower quantification limit of the assays. It allows an estimate of the correlation between the two response variables and takes into account this correlation for the estimation of other model parameters. This model was applied in a large cohort study (APROCO Cohort) to study the evolution under antiretroviral treatment of the two major biomarkers of the progression of Human Immunodeficiency Virus (HIV) infection: plasma HIV RNA and CD4+ T lymphocytes cell count. In a sample of 929 patients who started an highly active antiretroviral therapy, we illustrate the superiority in terms of likelihood of a bivariate model compared to two univariate models and the impact of taking into account the left-censoring of HIV-RNA. Moreover, interpretation of the model parameters allows confirmation of correlation between these two markers throughout the whole follow-up and the continuous decrease of plasma HIV RNA on average. Despite some limitations (distribution assumption, ignorance of missingness process), such a model appeared to be very useful to correctly describe the current evolution of important biomarkers in HIV infection.

CD4 Lymphocyte Count↗

PubMed2003

Progression of renal disease measured by the reciprocal of serum creatinine.

BACKGROUND: This study aims to quantify the decrease in the reciprocal of serum creatinine during the two years prior to the start of dialysis and to identify the factors associated with the progression of renal disease. METHODS: The study included 76 patients who were monitored for an average of 26.27 months. During the study 52 patients began dialysis treatments. The clinical and analytical variables were analyzed using the t-student test, ANOVA or the Kruskall-Wallis test. A multiple regression analysis was carried out with the decrease in the reciprocal of serum creatinine as the dependent variable. RESULTS: There was a decrease between the mean value during the two years prior to dialysis, the mean value during the previous year and the value at the start of dialysis treatments of 0.29, 0.21 and 0.17 respectively. The nephropathy having the sharpest drop in the reciprocal of serum creatinine, expressed as a percentage of the initial value, was found to be nephroangiosclerosis (46.29%). A greater decline in the reciprocal of serum creatinine was exhibited by low albumin values and adjusted by means of different variables with LDL levels (p = 0.141). For different levels of haemoglobin, proteinuria and cholesterol, the drop in the reciprocal of serum creatinine was greater in patients having a diastolic blood pressure reading of 90 or greater. CONCLUSIONS: The decrease in the reciprocal of serum creatinine was associated with different variables in patients who required dialysis.

Adult↗

PubMed1996

Variability of gastrointestinal transit in healthy women and men.

BACKGROUND AND AIMS: Measurements of gastrointestinal transit are made in clinical and research gastroenterology, yet their intrinsic variability is not well characterised. In particular, an influence of hormones on transit has been proposed as the basis for gastrointestinal symptoms that vary with the menstrual cycle. Our aims were to quantify individual differences in transit during the menstrual cycle in healthy women and to compare these with the intrinsic variability in healthy men. METHODS: On two occasions, whole gut transit was assessed scintigraphically and colonic transit quantified by radio-opaque markers. Thirty two healthy volunteers (12 women, 20 men) were studied, women during the follicular and luteal phases, men twice within a similar four week period. Diets and exercise were standardised prior to and during both studies. RESULTS: Colonic transit was significantly faster in men, and postlag gastric emptying was also more rapid; other indices of regional transit were not different between the sexes. Total colonic transit time was equally well reflected by the scintigraphic and radio-opaque marker methods. Important intraindividual differences were noted in both sexes. The variances in our samples predicted an 80% chance of detecting (with 95% confidence) a mean effect of menstrual hormones on transit that was in the same range as the intrinsic variation in men. CONCLUSIONS: Colonic transit was faster in men than in women. Although group means in the two studies were almost identical, single assessments of transit in subjects sometimes exhibited considerable variability, implying broad biological variations. Given this intrinsic variability, the influence of menstrual hormones on gastrointestinal transit must be small and of doubtful clinical significance.

Adult↗

PubMed2002

TPMT in the treatment of Crohn's disease with azathioprine.

Azathioprine induced profound myelosuppression linked to TPMT deficiency has now been documented in many patient groups, including those with Crohn's disease. At the start of azathioprine or mercaptopurine therapy, measurement of TPMT activity has a role in identifying the 1 in 300 patients who are at risk of severe myelosuppression when treated with standard thiopurine dosages. During the initial months of azathioprine therapy a knowledge of TPMT status warns of early bone marrow toxicity. In patients established on azathioprine these is no clear evidence to suggest that TPMT is predictive of clinical response or drug toxicity, indicating a role for TPMT in the prediction of early events rather than long term control. In patients with Crohn's disease on long term azathioprine therapy, it is clear that myelosuppression, particularly leucopenia, is caused by other factors in addition to variable TPMT activity and therefore monitoring of blood cell counts throughout treatment is essential.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1993

Biological markers of intermediate outcomes in studies of indoor air and other complex mixtures.

Biological markers of intermediate health outcomes sometimes provide a superior alternative to traditional measures of pollutant-related disease. Some opportunities and methodologic issues associated with using markers are discussed in the context of exposures to four complex mixtures: environmental tobacco smoke and nitrogen dioxide, acid aerosols and oxidant outdoor pollution, environmental tobacco smoke and radon, and volatile organic compounds. For markers of intermediate health outcomes, the most important property is the positive predictive value for clinical outcomes of interest. Unless the marker has a known relationship with disease, a marker response conveys no information about disease risk. Most markers are nonspecific in that various exposures cause the same marker response. Although nonspecificity can be an asset in studies of complex mixtures, it leads to problems with confounding and dilution of exposure-response associations in the presence of other exposures. The timing of a marker's measurement in relation to the occurrence of exposure influences the ability to detect a response; measurements made too early or too late may underestimate the response's magnitude. Noninvasive markers, such as those measured in urine, blood, or nasal lavage fluid, are generally more useful for field studies than are invasive markers. However, invasive markers, such as those measured in bronchoalveolar lavage fluid or lung specimens from autopsies, provide the most direct evidence of pulmonary damage from exposure to air pollutants. Unfortunately, the lack of basic information about marker properties (e.g., sensitivity, variability, statistical link with disease) currently precludes the effective use of most markers in studies of complex mixtures.

Aerosols↗

PubMed2006

Pulmonary intra-alveolar siderophages in SIDS and suffocation: a San Diego SIDS/SUDC Research Project report.

Pulmonary intra-alveolar siderophages (PS) have been suggested as a marker of previous attempts at imposed suffocation in infants dying suddenly and unexpectedly. The aims of this study were to (1) compare PS counts between cases of sudden infant death syndrome (SIDS) and a control group comprised of infants whose deaths were attributed to accidental or inflicted suffocation, (2) compare clinical variables in SIDS and control suffocation cases, and (3) review individual cases irrespective of the cause and manner of death with an average PS count greater than 200 per 20 high-power fields (hpf) per lung lobe. Retrospective assessment of siderophages in available iron-stained lung sections was undertaken in 91 SIDS cases and 29 cases of death due to suffocation (27 accidents and 2 homicides) from the San Diego SIDS and Sudden Unexplained Death in Childhood (SUDC) Research Project (SDSSRP) database. Neither the means of the log-transformed PS counts nor the medians of the raw PS counts were significantly different between the SIDS and control suffocation groups. The distributions of the PS data were different, however-the range was wider in the SIDS group. Only 6% of each group had a history of prior apparent life-threatening events. Approximately three fourths of the families from both groups had no prior referral to Child Protective Services. The number of PS varies widely in cases of sudden infant death caused by SIDS and accidental or inflicted suffocation and cannot be used as an independent variable to ascertain past attempts at suffocation.

Asphyxia↗

PubMed1999

Quantitative analysis of constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1B1 expression in human lymphocytes.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) results in a broad spectrum of biological responses, including altered metabolism, disruption of normal hormone signaling pathways, reproductive and developmental effects, and cancer. Cytochrome P450 1B1 (CYP1B1) is a dioxin-inducible gene that is active in the formation of 4-hydroxyestradiol, a potentially genotoxic catechol estrogen. Therefore, the analysis of CYP1B1 in humans may be useful in establishing relationships between dioxin exposure and adverse health effects. In this study, we examined the expression of CYP1B1 in human peripheral blood lymphocytes of unexposed individuals using a quantitative reverse transcription-PCR method. Absolute CYP1B1 RNA levels varied more than 30-fold in uncultured mononuclear cells obtained from 10 individuals. In vitro treatment of mitogen-stimulated lymphocytes with TCDD for 1-5 days of culture resulted in a peak induction of CYP1B1 after 3 days. The induction of CYP1B1 RNA levels after 3 days of culture was dose-dependent, exhibited a maximum response above 10 nM TCDD, and varied greatly among different individuals. However, the half maximal dose required for this induction was similar between individuals and comparable to that observed in the MCF-7 and HepG2 human cell lines. These observations indicate that CYP1B1 exhibits variable constitutive expression and is inducible in vitro by TCDD in human lymphocytes and that the magnitude of induction varies within the population. These data define the suitability of CYP1B1 for use as a mechanistically based biomarker in ongoing molecular epidemiological studies of human populations exposed to dioxins and related chemicals that bind the aromatic hydrocarbon receptor.

Adult↗

PubMed2000

The influence of parity and gravidity on first trimester markers of chromosomal abnormality.

We have studied changes in first trimester fetal nuchal translucency (NT) and maternal serum free beta-hCG and PAPP-A with gravidity and parity in 3252 singleton pregnancies unaffected by chromosomal abnormality or major pregnancy complications. We have shown that gravidity and parity is associated with a small but progressive decrease in fetal NT and a small but progressive increase in free beta-hCG and PAPP-A. None of these small changes with increasing gravidity or parity are statistically significant and hence correction for these variables is not necessary when considering first trimester screening for chromosomal abnormalities.

Adult↗

PubMed2002

NM23 expression as prognostic factor in colorectal carcinoma.

BACKGROUND: The current most important prognostic indicator in colorectal carcinoma is tumor stage at the moment of diagnosis. The role of NM23 gene as prognostic factor is controversial. The aim of this study was to investigate NM23 expression. PATIENTS AND METHODS: The study population included 104 unselected patients who underwent surgery for colorectal carcinoma between 1992 and 1997. NM23 expression was quantified by estimating the percentage of tumor cells with unequivocal reactivity. The percentage was scored: 0 when no tumor cells showed immunoreactivity; 1 when less than 10% of cells showed immunoreactivity; 2 when 11-50% of cells were positive; 3 when more than 51% of cells were positive. RESULTS: Four cases belonged to group 0.21 to group 1.55 to group 2 and 24 to group 3. CONCLUSION: NM23 cannot be considered an independent prognostic variable.

Antigens, Neoplasm↗

PubMedDate not supplied

[Cytogenetic variants of dysregenerative and precancerous epithelial changes in chronic inflammatory pulmonary diseases].

Surgical material of the lungs and their parts from 31 patients and open biopsies were studied. Proliferative activity (Ki-67, PCNA) and oncomarkers expression (bcl-2, p-53, c-myc, b-TGF, chromogranin-A) were studied immunohistochemically in the foci of various epithelial changes. It is established that a wide spectrum of alterations in pulmonary tissue is associated with variability of precursor cells and may have nosological features.

Adolescent↗

PubMed2004

Validation of plasma fibrinogen as a marker of carotid atherosclerosis in subjects free of clinical cardiovascular disease.

BACKGROUND AND OBJECTIVES: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. The aim of this study was to validate the measurement of plasma fibrinogen as a marker of subclinical atherosclerosis in a series of asymptomatic subjects (n=519, median age 55.5 years, 80% men). DESIGN AND METHODS: All individuals had a complete clinical examination, lipid profile (cholesterol and its high and low density lipoprotein fractions and triglycerides), global vascular risk assessment (PROCAM), and B-mode ultrasonography of the carotid arteries to determine the intima-media thickness (IMT) and the presence of atheroma plaques. C-reactive protein (CRP), and von Willebrand factor (vWF) were also measured in all subjects as markers of inflammation/endothelial damage. RESULTS: In the univariate model, a positive relationship was found between plasma fibrinogen concentration and carotid IMT (p<0.001). Fibrinogen concentration also correlated positively with age (p<0.001), systolic blood pressure (p<0.001), smoking (p<0.05), diabetes (p<0.05), PROCAM (p<0.001), CRP and vWF (p<0.001). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p=0.008) after adjustment for all parameters analyzed. INTERPRETATION AND CONCLUSIONS: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen levels was related to carotid IMT independently of a wide range of important confounding variables. Plasma fibrinogen may represent a systemic marker of carotid atherosclerosis.

Adult↗

PubMed2006

MIB-1 and MCM-2 immunohistochemical analysis does not aid in identification of serrated colorectal polyps with abnormal proliferation.

We investigated the staining characteristics of serrated polyps with abnormal proliferation (SPAP) using MIB-1 and MCM-2 to determine if they could provide assistance in delineating SPAPs from traditional hyperplastic polyps (HPs). Using published morphologic criteria we reviewed H&E slides of 107 polyps from 80 patients. Thirty-nine (36.4%) polyps met the criteria for SPAP Within a given region, polyps in the transverse colon had the largest percentage of SPAPs (50.0%) followed by the right colon (40.9%). The majority of SPAPs (82.1%) and HPs (72.1%) showed MIB-1 staining confined to the basal third of the crypts. The majority of SPAPs (59.0%) and HPs (52.9%) showed MCM-2 staining extending into the apical third of the crypts. We do not recommend MIB-1 or MCM-2 staining to differentiate SPAPs from conventional HPs, since staining characteristics are not significantly different between the 2 groups, and frequent variable crypt staining within a given polyp is difficult to interpret.

Biomarkers, Tumor↗

PubMedDate not supplied

Cyclooxygenase-2 (cox-2) expression and angiogenesis in intracranial ependymomas.

AIM: Cyclooxygenase-2 (Cox-2), the inducible key enzyme in the biosynthesis of prostaglandins, appears to play a role in the regulation of progression, invasiveness and angiogenesis of various neoplasms including some glial tumors. Little is known about the role of Cox-2 in angiogenesis and proliferation of ependymomas. We studied Cox-2 expression, Ki-67 labeling index (Ki-67 LI) and microvessel density (MVD) in 30 intracranial ependymomas and analyzed the relationship among these parameters to evaluate their importance in the tumor biology of ependymomas. RESULTS: The mean Ki-67 LI for all tumors ranged from 1 - 50% (mean 9%). Statistically significant difference was present for Ki-67 LI between ependymomas (grade II, WHO) and anaplastic ependymomas (grade III, WHO) (p < 0.001) (mean Ki-67 LI for ependymoma, 2.8%, for anaplastic ependymomas, 15.6%). Anaplastic ependymomas did not demonstrate a greater vascularization than ependymomas, and the MVD values were 84.5 +/- 39.7 for ependymomas, and 90.6 +/- 61.4 for anaplastic ependymomas. Cox-2 immunohistochemical expression was observed in 19 tumors (63%). Although Cox-2 expression was slightly higher in anaplastic ependymomas, it was not statistically significant. No correlation was found between Cox-2 expression and MVD and Ki-67 LI. CONCLUSION: Similar to morphologic and prognostic heterogeneity in ependymomas, Cox-2 expression, MVD and Ki-67 LI also show a great variability. Other factors may be more important for the proliferation and angiogenesis of ependymomas.

Adolescent↗

PubMed1995

[The malignancy potential of colorectal polyps--histomorphometric, histochemical and immunohistochemical study of the dysplasia-carcinoma sequence].

Colorectal polyps are usually diagnosed endoscopically and are simultaneously removed. Since adenomatous polyps tend to become malignant, these deserve special attention. In order to prevent carcinomas arising from pre existing adenomas, a precise analysis of the lesions in the mucous membrane of the polyps with regard to their malignancy potential is very important. Morphometric methods and determination of proliferation kinetics enable the dignity of a neoplasia to be assessed. Sporadic colorectal polyps were examined to what extent the morphometric analysis of nuclear area, the silver staining of nucleolar organizer regions (AgNORs) and the immunohistochemical staining of the Ki67 antigen permit further differentiation of the growth pattern of the tumor. Tissue from 50 hyperplastic polyps, 50 tubular and 50 tubulovillous adenomas was endoscopically removed and investigated, whereas pure villous adenomas were not examined due to their relative infrequency. These tissues were compared with biopsies of normal colonic mucosa and also with invasive adenocarcinomas. The Ki67 score shows that the proliferative activity is not significantly different between normal colonic mucosa and hyperplastic polyps, however there is a noticeable difference between the proliferation of the former types and colorectal neoplasias. The staining of the NORs does not reveal differences between the various grades of dysplasia in the adenomas, and therefore proves to be inadequate for differentiation, whereas morphometric and immunohistochemical measurements reveal appreciable selectivity. No correlation is observed between the parameters from the morphometric, histochemical and immunohistochemical analysis. Using the methods mentioned above the dysplasia-carcinoma-sequence can be clearly differentiated, however the validity of the different measurements is very variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1993

Clinical, biological and histological considerations on primary intracranial germinomas in the prevalent sites.

Twenty-four germinomas from which tumor sites were 11 pineal, 7 suprasellar, and 6 basal ganglial and thalamic (BG-T) were subjected. Humoral tumor markers of HCG, CEA and AFP were measured and compared with immunohistochemistries for these tumor markers along with PLAP, HPL and PKK1. Humoral tumor markers and immunohistochemistries did not always comprehend to each other. Difference of the survival rates among tumor sites was thought to be attributed to the variabilities in their histological, immunochemical and flow cytometric results.

Adolescent↗

PubMed2026

DNA methylation biomarkers for early detection of ovarian cancer.

Ovarian cancer (OC) remains difficult to detect at an early stage, and current screening approaches using CA125 and transvaginal ultrasonography have not demonstrated sufficient benefit for population screening. DNA methylation is a promising biomarker class because epigenetic alterations may arise early in tumourigenesis, can be detected in circulating cell-free DNA (cfDNA), and may provide tissue-of-origin information. This review critically evaluates recent evidence on DNA methylation biomarkers for early OC detection. PubMed/MEDLINE, Web of Science, and Scopus were searched for studies published between January 2020 and September 2025, supplemented by selected earlier studies of biological or methodological relevance. Evidence was synthesised across single-gene biomarkers, multi-locus panels, genome-wide signatures, assay platforms, and machine-learning classifiers, with emphasis on early-stage performance, histological representation, comparator populations, analytical methodology, and validation design. Single-gene markers such as BRCA1, RASSF1A, OPCML, HOXA9, and HIC1 show variable performance, while multi-gene and classifier-based approaches generally provide stronger discrimination. However, many studies remain limited by retrospective case-control designs, small FIGO stage I-II subsets, predominance of serous disease, and insufficient prospective validation. Integration with CA125 may improve sensitivity but can reduce specificity, which is critical in low-prevalence screening. Clinical translation will therefore require minimal and reproducible methylation signatures, standardised low-input cfDNA workflows, rigorous external validation, and prospective longitudinal evaluation in intended-use populations.

Humans↗

PubMed2004

A Mediterranean dietary style influences TNF-alpha and VCAM-1 coronary blood levels in unstable angina patients.

BACKGROUND: A Mediterranean dietary pattern has been associated with a reduced risk of coronary heart disease, as well as a reduction of oxidative stress, but studies indicating possible interactions between food intake and inflammatory mediators production at specific sites are lacking. AIM OF THE STUDY: To assess the relationship between Mediterranean diet consumption and inflammatory related molecules production in coronary vessels. METHODS: A previously reported Mediterranean-diet score was computed summing-up the quintiles of eight dietary components from a validated food frequency questionnaire in 24 patients with unstable angina. Tumor necrosis factor (TNF-alpha) and vascular cell adhesion molecule (VCAM-1) concentrations were measured in coronary sinus blood. RESULTS: Both biomarkers showed an inverse association with the Mediterraneandiet score. The association between VCAM-1 and the Mediterranean-diet score had an adjusted beta coefficient of -35.1 ng/ml (95% coefficient interval, CI: -63.5 to -6.7). The adjusted beta coefficient using TNF-alpha as the dependent variable was -41.6 pg/ml (95 % CI: -76.2 to -7.1). The consumption of olive oil as a single item showed a significant inverse association, and a Mediterranean-diet score excluding olive oil was also inversely associated with TNF-alpha and VCAM-1 serum levels in coronary venous blood. CONCLUSIONS: Adherence to a Mediterranean dietary pattern may protect against coronary artery wall production of inflammatory mediators. This finding could provide a novel mechanistic explanation for the recognized lower coronary risk associated with a Mediterranean diet.

Angina, Unstable↗

PubMed1998

Evaluation of intra- and interindividual variation of urinary 1-hydroxypyrene, a biomarker of exposure to polycyclic aromatic hydrocarbons.

The study was performed on 30, 8-year-old children living in an industrial town of the Upper Silesia region. Morning urine samples were collected on 6 consecutive days. Intraindividual variation of urinary 1-hydroxypyrene concentrations, calculated as a coefficient of variance (CV), ranged from 14 to 109% whereas inter-individual variation ranged from 69 to 109%. Three-way analysis of variance disclosed a significant effect of sex, exposure to environmental tobacco smoke and day of examination on 1-hydroxypyrene concentrations not corrected for creatinine. The appropriate sample size for population studies and the minimum number of observations for the individual assessment of environmental exposure to PAHs calculated on the basis of inter- and intraindividual variability of 1-hydroxypyrene concentrations in urine amounted to 164 and 99, respectively. Urinary 1-hydroxypyrene may be considered a good indicator of environmental exposure to PAHs at the group level.

Biomarkers↗