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Results for “Biomarker variability”

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At least 703 records · Page 39Linked to original sources

PubMed2006

A fast, simple, and inexpensive method to collect exhaled breath condensate for pH determination.

BACKGROUND: Exhaled breath condensate (EBC) analysis is a noninvasive method for assessing lower airway inflammation. Various methods of collecting EBC have been described. However, they are often time-consuming or involve expensive equipment. OBJECTIVE: To evaluate the efficiency and repeatability of a simple, fast, and inexpensive method of EBC collection for pH determination. METHODS: Twenty-four mild asthmatic patients, 18 moderate-to-severe asthmatic patients, and 26 controls were asked to slowly exhale for 45 seconds into a -80 degrees C cooled metal cylinder covered with protective rubber and attached to a piece of tubing. The EBC was collected using a syringe's plunger. The groups were compared regarding EBC pH. Reproducibility tests were also performed. Induced sputum samples were obtained for inflammatory cell counts. RESULTS: We obtained approximately 50 microL of EBC for pH determination. Mild asthmatic patients had lower mean +/- SD pH values than controls (5.97 +/- 0.48 vs 6.36 +/- 0.34; P = .008), and corticosteroid-treated, moderate-to-severe asthmatic patients had mean +/- SD pH values similar to controls (6.23 +/- 0.38; P > .05). Mean +/- SD sputum eosinophil percentages were higher in both asthmatic groups than in controls (3.42% +/- 5.37% and 4.14% +/- 4.98% vs 0.04% +/- 0.12%; P < .001) and were not correlated with pH values in all groups. The mean intraday coefficient of variation for the method was 4.8% (range, 0.9%-8.8%). No correlation was found in all groups between sputum neutrophils and pH. CONCLUSIONS: We developed a useful device for collecting EBC for pH evaluation that could provide an alternative to other methods when pH is the main variable evaluated.

Adolescent↗

PubMed2002

Plasma adiponectin levels in overweight and obese Asians.

OBJECTIVE: Hypoadiponectin has been documented in subjects with obesity, diabetes mellitus, or coronary heart disease, suggesting a potential use of plasma adiponectin in following the clinical progress in subjects with metabolic syndrome (MS). In this study, we investigated the plasma adiponectin levels in relation to the variables of MS among overweight/obese Asian subjects. RESEARCH METHODS AND PROCEDURES: The plasma adiponectin, anthropometric and biochemical measurements, oral glucose tolerance tests (OGTT), and modified insulin suppression tests were performed on 180 overweight/obese Asian subjects [body mass index (BMI) >or= 23 kg/m(2)], including 47 subjects with morbid obesity (BMI >or= 40 kg/m(2)). RESULTS: The plasma adiponectin levels negatively correlated with BMI, waist-to-hip ratio, fasting plasma glucose, insulin, triglyceride, uric acid levels, hyperinsulinemia, and glucose intolerance in OGTT, but positively with high-density lipoprotein-cholesterol. In contrast, they were not related to blood pressure and total cholesterol. Moreover, insulin sensitivity, measured by quantitative insulin sensitivity check index (QUICKI) or in insulin suppression tests, significantly correlated with the plasma adiponectin levels. Among morbidly obese subjects, only the waist-to-hip ratio correlated with the plasma adiponectin levels. Using multivariate linear regression models, the area under curve of plasma glucose in OGTT and high-density lipoprotein-cholesterol among the overweight/obese subjects and WHR among the morbidly obese subjects were significantly related to the plasma adiponectin levels after adjustment for other variables. DISCUSSION: In overweight/obese Asians, the plasma adiponectin levels significantly correlated with various indices of MS except hypertension. Whether the plasma adiponectin level could be a suitable biomarker for following the clinical progress of MS warrants further investigation.

Adiponectin↗

PubMed1990

Constructing an instrument to measure the rate of aging in female pigtailed macaques (Macaca nemestrina).

To develop a battery of innocuous tests measuring individual differences in the rate of biological aging, longitudinal data were gathered on 28 biochemical, physiological, and morphological characteristics of 40 adult female pigtailed macaques. The change in each variable over time, i.e., the beta coefficient of linear regression, was calculated for each animal, and a matrix of correlations among the variables was constructed. Eight variables correlated well with the first principal component of the matrix. These variables (rate of fingernail growth, blood lymphocytes, mean corpuscular hemoglobin, immunoglobulin A, and serum sodium, chloride, total protein, and creatinine) represented the best subset of the potential biomarkers analyzed to produce an index covering a range of morphologic and functional systems that change with age. A similar set representing a wider range of systems and measured over a larger fraction of the life span should provide a valid index of an individual's rate of biological aging.

Aging↗

PubMed2000

Albumin as an outcome measure in haemodialysis in patients: the effect of variation in assay method.

BACKGROUND: Serum/plasma albumin is an important predictor of future mortality/morbidity in haemodialysis (HD) patients and has been proposed as an important audit measure. Different methods of albumin assay give different results and the bias between methods may be greater in renal failure patients. METHODS: Albumin concentration in plasma was measured by three methods, two dye-binding methods (bromocresol green (BCG) and bromocresol purple (BCP)) and an immuno-turbidimetric (ITM) method, in 143 HD patients (group I) and 49 non-renal patients (group II). Comparisons were made between means, variation in differences across a range of albumin concentrations and on the percentage of patients within the normal range. RESULTS: In HD patients (group I), BCG over-estimated plasma albumin compared with the other two methods. The difference could be as much as 10 g/l and was more marked in hypoalbuminaemic patients. The BCP method gave results closer to the ITM method, particularly in HD patients. These differences were less marked in group II patients but both methods overestimated albumin compared with the ITM method. Using the BCG local laboratory normal range, 84% of HD patients had plasma albumin concentrations within the normal range but this fell to 57% if the BCP results were used. CONCLUSIONS: The method for determining albumin concentration has a marked effect on the results particularly in HD patients. BCG, the most commonly used method, gives higher results than other methods and correlates poorly with an immunological method. These differences make comparative audit between nephrology units difficult and have implications for other biochemical variables and other specialties.

Biomarkers↗

PubMed2000

Relationship of N-acetyl-beta- glucosaminidase levels to seriousness of suicide attempts.

We hypothesized that levels of N-acetyl-beta-glucosaminidase (NAG) would differ between patients making serious versus nonserious suicide attempts. The levels of NAG from 11 patients hospitalized for serious suicide attempts were compared to 5 patients whose suicide attempts were not rated serious. There was a significant difference in the mean NAG levels of the serious suicide attempters and the nonserious attempters (23 versus 52; p = 0.01). NAG may be a marker for a biological variable that is associated with the seriousness of a suicide attempt.

Acetylglucosaminidase↗

PubMed1992

Prostate-specific antigen test: operating characteristics and assessment criteria in the diagnosis of prostatic cancer.

The sensitivity and specificity of prostate-specific antigen (PSA) in prostatic carcinoma is of considerable interest. In this study, we have assessed PSA and also correlations between positive and negative predictive values of PSA and the prevalence of prostatic cancer. Firstly, cutoff point must be selected as a positivity criterion for prostatic cancer, according to the purpose of the test. Besides sensitivity, all the other operating characteristics are dependent upon the prevalence of the disease. Specificity and positive predictive value increase while negative predictive value decreases when prevalence increases. As the relationship between the age and the prevalence of prostatic carcinoma is well known, the age of the patient becomes a variable of prominent importance when assessing the test.

Aged↗

PubMed2003

Relationship of arachidonic acid concentration to cyclooxygenase-dependent human platelet aggregation.

Inhibition of ex vivo arachidonic acid (AA)-induced aggregation is a biomarker for the isotype selectivity of cyclooxygenase (COX) inhibitors since platelets express COX-1 but not COX-2. At low concentrations, there is broad inter- and intrasubject variability in AA-induced aggregation of platelets ex vivo. This study defined a concentration that reliably induces aggregation without overcoming inhibition by therapeutic aspirin therapy (ASA, 81-mg) treatment. Logistic regression analysis of ex vivo aggregation, induced with increasing concentrations of AA in platelet-rich plasma (PRP), estimated that platelets from > or = 90% of subjects would aggregate at > or = 1.5 mM AA (95% confidence interval [CI], 1.1, 2.1). A concentration of 1.6 mM AA failed to aggregate platelets from 26 healthy volunteers, who had previously aggregated at this concentration, following six daily oral doses of 81 mg of ASA. These data demonstrate that 1.6 mM AA reproducibly induces platelet aggregation in PRP from healthy volunteers without overcoming the antiplatelet effect of daily low-dose aspirin therapy.

Adolescent↗

PubMed2004

Low-grade lymphoma.

Folicular lymphoma (FL), the second most common subtype of non-Hodgkin lymphoma, shows considerable heterogeneity in its clinical behavior, representative of a biology that appears increasingly complex and diverse. As our knowledge of the molecular basis of FL increases, we strive for an integration between the bench and clinic that yields treatments based on our scientific understanding and biomarkers that allow us to prescribe treatment rationally. In Section I, Dr. Randy Gascoyne describes the histologic, cytogenetic and biologic features of FL that underlie its clinical variability. Key aspects of the pathologic diagnosis of FL that have particular relevance to the clinician are highlighted. A proposed model for follicular lymphomagenesis and diffuse large B cell lymphoma transformation has emerged and continues to evolve as the molecular story unfolds. A biologic basis for clinical outcome in FL also appears to be forthcoming. In Section II, Dr. Jane Winter addresses the complex process of selecting among the many treatment options for patients with FL. Previously a simple matter of deciding between oral or intravenous alkylators, clinicians and patients must now struggle to choose among vastly different approaches ranging from "watch and wait" to stem cell transplantation. The introduction of rituximab and radioimmunoconjugates is changing the treatment paradigm, but the optimal approach to integrating these and other new agents remains to be determined. At every decision point, the best approach is always a clinical trial. In Section III, Dr. Koen Van Besien provides a well-documented update on outcomes associated with autologous and allogeneic stem cell transplantation for FL. The results of trials of autologous stem cell transplantation in first remission and recent data supporting a role for graft purging are discussed. Based on the premise that a graft-versus-lymphoma effect is operative in FL, reduced-intensity allogeneic transplantation is the preferred approach in many cases, and recently reported results are summarized. Criteria for patient selection and the optimal role of transplantation in the overall therapeutic plan for the patient with FL are presented.

Antineoplastic Agents↗

PubMed1997

Evaluation of the lactulose/mannitol and 51Cr-ethylenediaminetetraacetic acid/14C-mannitol methods for intestinal permeability.

BACKGROUND: We earlier compared the lactulose/mannitol and 51Cr-ethylenediaminetetraacetic acid (EDTA)/14C-mannitol methods for intestinal permeability We have now investigated an increased number of control subjects, with special regard to the influence of urinary volume, sex, age, and smoking on marker excretion, and patients with intestinal disorders, with special regard to correlations between markers. METHODS: The 0- to 6-h urinary excretion of orally administered markers was measured in 65 control subjects and in 70 patients. RESULTS: In the control group excretion of mannitol and 14C-mannitol (small-pore permeability markers) was strongly correlated to urinary volume, whereas such correlation was weak for lactulose and absent for 51Cr-EDTA (large-pore permeability markers). No sex difference in marker excretion was found, but correlation to urinary volume was more pronounced in males. There was a slightly decreasing excretion of markers with increasing age, reaching significance for 51Cr-EDTA and 14C-mannitol; their excretion ratio was unaffected. Smoking did not significantly affect marker excretion. In the patient group the excretion of large-pore markers tended to be higher and that of small-pore markers to be lower than in the control group; correlation between the large-pore markers, between the small-pore markers, and between the large-pore/small-pore marker ratios was higher than in the control group. CONCLUSIONS: Correction for urinary volume substantially reduces variability in small-pore marker excretion. Excretion of both types of markers tends to decrease with age, the large-pore/small-pore marker ratio remaining unchanged. Smoking does not affect small-intestinal permeability. 14C-mannitol is preferred to chemically determined mannitol owing to lower test variability.

Adolescent↗

PubMed1999

[Subependymal giant cell astrocytoma associated with tuberous sclerosis exhibiting rapid regrowth after 17 years: a case report].

A 17-year-follow-up case of subependymal giant cell astrocytoma (SGCA) is reported. In 1979, when aged 28 years, the patient first presented obstructive hydrocephalus caused by a tumor in the right lateral ventricle close to the foramen of Monro. It was partially removed by a transcallosal approach. Pathological examinations showed gemistocytic astrocytoma or SGCA associated with tuberous sclerosis. A ventriculo-peritoneal shunt was carried out and 36Gy of radiation therapy was administered. Eight months later, the patient suffered from an intraventricular hemorrhage originating from SGCA, but he responded to conservative therapy. He was followed-up by CT scans over 17 years. In 1996, because of rapid regrowth of the tumor, total removal was performed by a transcortical approach via the right frontal horn. The pathological diagnosis was SGCA. The greater part of the recurrent tumor was composed of blood vessels. The tumor cells were grouped into two morphological types, large cells and spindle cells. We compared the tumor in 1996 with that in 1979, each revealing immunohistochemical stainability for glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE) and S-100 protein (S-100). The large cells in 1979 were negative for GFAP, NSE and S-100, but were positive for NSE and S-100 in 1996. The spindle cells in 1979 were positive for GFAP, NSE and S-100, but were negative for GFAP in 1996. The pathological origin of SGCA remains a subject of controversy. These results suggest that the origin of SGCA could be variably differentiated cells like the germinal matrix cells.

Biomarkers, Tumor↗

PubMed2000

Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin lymphoma: a single-institution study of 200 patients.

High serum concentrations of vascular endothelial growth factor (S-VEGF) and basic fibroblast growth factor (S-bFGF) are associated with unfavorable clinical characteristics in cancer. The combined effect of S-VEGF and S-bFGF on the survival of 200 patients with non-Hodgkin lymphoma (NHL) was studied. High S-VEGF and S-bFGF at diagnosis were associated with poor survival with the medians, the highest tertiles, or the highest quartiles as the cutoff values. The highest prognostic power was obtained when S-VEGF and S-bFGF were examined as a combination. Patients who had both S-VEGF and S-bFGF within the highest quartiles had only a 21% 5-year survival rate in contrast to a 64% 5-year survival rate among patients with both factors within the 3 lowest quartiles (P <.0001). Simultaneous elevation of S-VEGF and S-bFGF was associated with poor survival in different grades of lymphomas and in the largest histologic subgroup, the large-cell diffuse and immunoblastic lymphomas. S-VEGF (relative risk [RR], 1.83; P =.019) and S-bFGF (RR, 2.02; P =.0049) had independent influences on survival in multivariate models when tested together with the components of the International Prognostic Index (IPI). Patients with both S-VEGF and S-bFGF within the highest quartiles had nearly 3 times higher risk for death (RR, 2.90; 95% confidence interval [CI], 1.56-5.40; P =.0008) than the rest of the patients. This RR was higher than the relative risks associated with any of the components of the IPI in the same model. The authors conclude that the combination of S-VEGF and S-bFGF is a powerful prognostic variable in NHL. (Blood. 2000;96:3712-3718)

Adult↗

PubMed1994

Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression.

HER-2/neu oncogene amplification and overexpression of breast cancer tissue has been correlated with poor prognosis in women with both node-positive and node-negative disease. However, several studies have not confirmed this association. Review of these studies reveals the presence of considerable methodological variability including differences in study size, follow-up time, techniques and reagents. The majority of papers with clinical follow-up information are immunohistochemical studies using archival, paraffin-embedded breast cancers, and a variety of HER-2/neu antibodies have been used in these studies. Very little information, however, is available about the ability of the antibodies to detect overexpression following tissue processing for paraffin-embedding. Therefore, a series of antibodies, reported in the literature or commercially available, were evaluated to assess their sensitivity and specificity as immunohistochemical reagents. Paraffin-embedded samples of 187 breast cancers, previously characterized as frozen specimens for HER-2/neu amplification by Southern blot and for overexpression by Northern blot, Western blot, and immunohistochemistry, were used. Two multitumor paraffin-embedded tissue blocks were prepared from the previously analyzed breast cancers as a panel of cases to test a series of previously studied and/or commercially available anti-HER-2/neu antibodies. Immunohistochemical staining results obtained with 7 polyclonal and 21 monoclonal antibodies in sections from paraffin-embedded blocks of these breast cancers were compared. The ability of these antibodies to detect overexpression was extremely variable, providing an important explantation for the variable overexpression rate reported in the literature.

Antibodies↗

PubMed1997

Osteoarthritis clinical trials: candidate variables and clinimetric properties.

Outcome assessment in osteoarthritis (OA) clinical trials requires the use of valid, reliable, and responsive measurement techniques. Clinical assessment procedures examine patient relevant issues, while imaging procedures and biologic marker assays probe different aspects of the underlying disease process. At present, there is no international agreement on which standardized procedures should be used in future studies or which domains should be included. Nevertheless, significant progress has been made in recent years toward attaining that goal and there are numerous measurement procedures, differing in their conceptual and clinimetric properties, from which to select a core set. The following review provides a description of candidate variables that merit consideration in reaching international harmonization on outcome measures for future OA clinical trials.

Biomarkers↗

PubMed1997

Dose reconstruction for individuals exposed to ionizing radiation using chromosome painting.

To be most useful, a biomarker for dose reconstruction should employ an end point that is highly quantitative, stable with time and easily measured. Reciprocal translocations have been shown to be a promising biomarker that is linked to both prior exposure and risk, and they can be measured easily and quantitatively using fluorescence in situ hybridization. In contrast to other biomarkers that are available, the frequency of reciprocal translocations in individuals exposed to whole-body radiation is stable with time after exposure, has rather small interindividual variability and can be measured accurately at low levels of exposure. Results from recent studies demonstrate that measurements of reciprocal translocation frequencies, facilitated by chromosome painting, can be used to reconstruct radiation dose for individuals exposed in the distant past.

Animals↗

PubMed2006

Short-term infliximab therapy improves symptoms of psoriatic arthritis and decreases concentrations of cartilage oligomeric matrix protein.

OBJECTIVE: The aim of the current study was to evaluate the short-term effects of anti-tumour necrosis factor alpha (infliximab) therapy on serum cartilage oligomeric matrix protein (COMP) levels, a possible biomarker of cartilage destruction. METHODS: Nine consecutive patients with active psoriatic arthritis (PsA) were treated with infliximab for 6 weeks. Serum COMP levels were measured and correlated to pre-established disease activity outcome variables: pain as assessed by the patient, using the 100 mm visual analogue scale (VAS), duration of morning stiffness (MGST), swollen joint count (SJC), tender joint count (TJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: Significant improvements in MGST, VAS, SJC and TJC values were observed after 6 weeks of therapy. Similar significant improvements were demonstrated in the ACR response rate and in eight (89%) patients the ACR20 was achieved. ESR and CRP decreased significantly over 6 weeks. Serum COMP levels also decreased significantly after 6 weeks of treatment (12.99 +/- 1.71 baseline, 10.22 +/- 1.1 after 6 weeks, P < 0.008). CONCLUSION: The results of our study suggest that short-term therapy with infliximab leads to decreased COMP levels in patients with PsA. COMP seems to be a good candidate for a biomarker reflecting cartilage response to this treatment in PsA patients.

Antibodies, Monoclonal↗

PubMed2006

Increase of plasma fibrinogen levels and variability with age in a sample of middle aged healthy men.

According to predictions from the current theoretical models for ageing the heterogeneity of the population is increasing with increasing age. Although the direct observation of such changes in humans is extremely difficult, supporting evidence should be identifiable in key biomarkers associated with health and mortality. Using data from the Northwick Park Heart Study II of 3052 healthy middle-aged men (mean 56 years of age, range 49-69 years), with 5 annual measures of CHD risk factors, ageing effects were tested for plasma fibrinogen, cholesterol and triglycerides. Fibrinogen levels increased with age (p < 0.0001), while cholesterol showed a decrease, and triglycerides did not show any change with age. There was a significant increase in the variance of fibrinogen with age (p < 0.0007) but not for cholesterol or triglycerides. The raising effect on fibrinogen levels associated with the A allele of the FIBB - 455G>A promoter variant also decreased with age (p = 0.005). The age-associated changes observed in the fibrinogen variability and the association of phenotype to genotype are discussed in light of the evolutionary theory, and their implications are considered.

Aged↗

PubMed1994

Validation of proliferation indices as surrogate endpoint biomarkers.

During the 1990s, research interest in the use of chemopreventive agents to reverse human colon carcinogenesis increased exponentially. In parallel, there has been an increase in the need for putative surrogate endpoint biomarkers (SEBs) of cancer risk. Since the hallmark studies of Lipkin et al. and Terpstra et al., among others, the rate and patterns of rectal mucosal proliferation have been established as intermediate biomarker endpoints for colon cancer risk, modulated by potential chemopreventive agents including calcium, wheat bran fiber, and nutritional stress diets. Researchers rely heavily on these rectal mucosal proliferation indices as surrogate endpoints to evaluate the relative efficacy of various chemopreventive intervention strategies. Standardization through quality control/quality assurance (QC/QA) programs which continuously validate the accuracy, reproducibility, and variability of these indices is increasingly needed. Along with many others, we have attempted to validate 3H-thymidine and bromodeoxyuridine labeling indices in rectal mucosal biopsies as reliable SEBs. In this manuscript we outline a series of QC/QA steps that can be followed in the validation process for new as well as "old" biomarkers prior to their use as primary efficacy surrogate endpoints for chemopreventive agent intervention trials.

Adenoma↗

PubMed2003

Peroxisome proliferation as a biomarker in environmental pollution assessment.

Peroxisome proliferators comprise a heterogeneous group of compounds known for their ability to cause massive proliferation of peroxisomes and liver carcinogenesis in rodents. In recent years it has become evident that other animals may be threatened by peroxisome proliferators, in particular aquatic organisms living in coastal and estuarine areas. These animals are exposed to a variety of pollutants of industrial, agricultural and urban origin which are potential peroxisome proliferators. Both laboratory and field studies have shown that phthalate ester plasticizers, PAHs and oil derivatives, PCBs, certain pesticides, bleached kraft pulp and paper mill effluents, alkylphenols and estrogens provoke peroxisome proliferation in different fish or bivalve mollusc species. The response appears to be mediated by peroxisome-proliferator activated receptors, members of the nuclear receptor family, recently cloned in fish. Based on these results it is proposed that peroxisome proliferation could be used as a biomarker of exposure to a variety of pollutants in environmental pollution assessment. This is illustrated by a case study in which mussels, used worldwide as sentinels of environmental pollution, were transplanted from reference to contaminated areas and vice versa. In mussels native to an area polluted with PAHs and PCBs, peroxisomal acyl-CoA oxidase (AOX) activity and peroxisomal volume density were 2-3 fold and 5-fold higher, respectively, compared to the reference site. When animals were transplanted to the polluted station, with increased concentration of organic xenobiotics, a concomitant significant increase of AOX was recorded. Conversely, in animals transplanted to the cleaner station, AOX activity and peroxisomal volume density decreased significantly. These results indicate that peroxisome proliferation is a rapid (i.e., two days) and reversible response to pollution in mussels. Before peroxisome proliferation can be implemented as a biomarker in biomonitoring programs, a well-defined protocol should be established and validated in intercalibration and quality assurance programmes. Furthermore, the influence of biotic and abiotic factors, some of which are known to affect peroxisome proliferation (season, tide level, interpopulation and interindividual variability), should be taken into consideration. The possible hepatocarcinogenic effects as well as the potential adverse effects on reproduction, development, and growth of peroxisome proliferators are unknown in aquatic organisms, thus providing a challenge for future investigations.

Acyl-CoA Oxidase↗