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PubMed2003

BNP as discharge criteria for heart failure.

BACKGROUND: Heart failure (HF) is a significant clinical and economic burden in the industrialized world. Advances in pharmaceutical compounds and various medical device technologies along with the use of sophisticated HF clinics have enhanced HF treatment and improved morbidity, mortality, and quality of life. However, hospital readmission rates remain stubbornly high. B-type natriuretic peptide (BNP) levels provide valuable information about a patient's chance of readmission within 30 days of discharge, making BNP a potentially useful tool for making discharge decisions and possibly reducing readmissions. METHODS: This review examines the strength and level of evidence in key areas to determine if BNP levels could be used as a guide for discharge of HF patients. Although most of the literature describes nonrandomized studies, there is general agreement that BNP levels can be measured accurately and precisely, that BNP levels reflect varying physiologic states, and that they predict outcomes. CONCLUSIONS: More studies are needed to determine extent of biologic variability. The further use of BNP as a potential discharge marker is promising but awaits additional randomized study that reflects use in a broad-based population.

Biomarkers↗
PubMed2006

Correlation analysis of two-dimensional gel electrophoretic protein patterns and biological variables.

BACKGROUND: Two-dimensional gel electrophoresis (2DE) is a powerful technique to examine post-translational modifications of complexly modulated proteins. Currently, spot detection is a necessary step to assess relations between spots and biological variables. This often proves time consuming and difficult when working with non-perfect gels. We developed an analysis technique to measure correlation between 2DE images and biological variables on a pixel by pixel basis. After image alignment and normalization, the biological parameters and pixel values are replaced by their specific rank. These rank adjusted images and parameters are then put into a standard linear Pearson correlation and further tested for significance and variance. RESULTS: We validated this technique on a set of simulated 2DE images, which revealed also correct working under the presence of normalization factors. This was followed by an analysis of p53 2DE immunoblots from cancer cells, known to have unique signaling networks. Since p53 is altered through these signaling networks, we expected to find correlations between the cancer type (acute lymphoblastic leukemia and acute myeloid leukemia) and the p53 profiles. A second correlation analysis revealed a more complex relation between the differentiation stage in acute myeloid leukemia and p53 protein isoforms. CONCLUSION: The presented analysis method measures relations between 2DE images and external variables without requiring spot detection, thereby enabling the exploration of biosignatures of complex signaling networks in biological systems.

Algorithms↗
PubMed1998

Using metal-ligand binding characteristics to predict metal toxicity: quantitative ion character-activity relationships (QICARs).

Ecological risk assessment can be enhanced with predictive models for metal toxicity. Modelings of published data were done under the simplifying assumption that intermetal trends in toxicity reflect relative metal-ligand complex stabilities. This idea has been invoked successfully since 1904 but has yet to be applied widely in quantitative ecotoxicology. Intermetal trends in toxicity were successfully modeled with ion characteristics reflecting metal binding to ligands for a wide range of effects. Most models were useful for predictive purposes based on an F-ratio criterion and cross-validation, but anomalous predictions did occur if speciation was ignored. In general, models for metals with the same valence (i.e., divalent metals) were better than those combining mono-, di-, and trivalent metals. The softness parameter (sigma p) and the absolute value of the log of the first hydrolysis constant ([symbol: see text] log KOH [symbol: see text]) were especially useful in model construction. Also, delta E0 contributed substantially to several of the two-variable models. In contrast, quantitative attempts to predict metal interactions in binary mixtures based on metal-ligand complex stabilities were not successful.

Algorithms↗
PubMed2001

Clinical significance of low-positive troponin I by AxSYM and ACS:180.

We compared troponin I (TnI) assays (AxSYM [Abbott]; ACS:180 [Bayer]) in blood samples with concentrations less than 10 ng/mL (< 10 micrograms/L). Discordant results were evaluated by linearity studies and by testing for rheumatoid factor. Patients with discordant TnI results were compared with patients with concordant results and patients with negative TnI who had a new myocardial infarction or died within 2 months of initial testing. Positive TnI cutoffs by AxSYM and ACS:180 were 0.7 ng/mL (0.7 microgram/L) and 0.13 ng/mL (0.13 microgram/L), respectively. We identified 173 specimens that were repeatedly positive by at least 1 assay; 143 specimens were positive by both assays. Twenty samples positive for TnI by AxSYM were negative by ACS:180, while 10 samples positive by ACS:180 were negative by AxSYM. The discordant samples showed no evidence of interfering substances, including rheumatoid factor. Clinical follow-up showed that 26% of patients with elevated TnI by both assays, 33% with TnI positive only by AxSYM, 22% with TnI positive only by ACS:180, and 8% with negative TnI by AxSYM encountered at least 1 clinical end point. Variable detection rates by these assays for low-positive TnI represent a clinically significant problem.

Aged↗
PubMed1999

Diagnosis of acute basophilic leukemia.

De novo acute basophilic leukemia (ABL) is a rare form of acute leukemia. Most frequently, the blast cells are morphologically undifferentiated, and the recognition of the presence of coarse basophilic granules may be the first step in diagnosis of this rare disorder. These granules are metachromatic and MPO negative. Immunophenotyping shows myeloid markers and some more specifically associated antigens such as CD9 or CD25 which are strongly expressed. Lymphoid, erythroid or megakaryocytic markers are not significantly expressed. In the absence of basophilic granules, some cases are classified as AML M0 if they express myeloid markers, or undifferentiated leukemia if no markers are present. If specific immature basophilic or theta granules are present, only an electron microscopic study will enable the diagnosis of a basophilic lineage assignment. Some cases may be misdiagnosed if all these steps are not followed. After all these investigations, two types of ABL may be defined: 1-A pure ABL, monophenotypic with basophilic lineage involvement alone, which should be classified as AML M8 . Genetic studies in these cases are very important for understanding the leukemic process and in a few cases, we can suspect c-MYB oncogene involvement but further investigations are still necessary. 2- More frequently, acute leukemia can be a mixture of blasts from different lineages with an important but variable participation of mature or immature basophilic cells. These cases must be classified as AML/Baso or multiphenotypic acute leukemias and often present Phl -chromosomal abnormality.

Biomarkers↗
PubMed2001

[Hypovitaminosis D in postmenopausal women with low bone mineral density].

BACKGROUND: Low vitamin D levels are a risk factor for osteoporosis. In the Northern hemisphere, a high frequency of low vitamin D levels has been detected. The correction of this deficit is associated with a lower fracture risk. AIM: To measure serum vitamin D levels in postmenopausal women with low bone mineral density. MATERIAL AND METHODS: 25-hydroxyvitamin D levels were measured in 40 postmenopausal women aged 50 to 74 years old, with a spine bone mineral density of less than 2 standard deviation of the values for young individuals. Serum calcium, phosphorus and calcium dietary intake were also measured. RESULTS: Mean serum 25-hydroxyvitamin D levels were 32.2 +/- 12.5 ng/ml. No correlation between vitamin D levels and other measured variables was observed. Using a cutoff value of 15 ng/ml, two women had low 25-hydroxyvitamin D levels. CONCLUSION: In this sample of postmenopausal women, vitamin D deficiency was infrequent.

Aged↗
PubMedDate not supplied

Hepatitis B vaccination awareness and biological risk.

BACKGROUND: Hepatitis B virus is a possible risk in persons exposed to biological risk at work. Vaccination is the only prevention against infection. OBJECTIVES: A population of 1,408 employees of the University of Padua was investigated to define the immunological status for HBV and degree of awareness to hepatitis B vaccination. METHODS: The subjects were subdivided according to sex, age (< or = 40 or > 40 years old), level of education (college graduates or lower), and the extent of biological risk (no risk, low or high risk). Clinical history questionnaires were used and measurement of hepatitis B markers was carried out. RESULTS: The results showed that only 30.5% of the subjects had been vaccinated; among these, 90.2% showed a measurable level of anti-HBs antibodies, 8.2% showed anti-HBs antibodies lower than 10 IU/L, and 1.6% showed positive markers of previous infection. However, among non-vaccinated subjects 13.4% were positive for previous infection; in all subjects, prevalence of hepatitis B virus infection was 9.8%. The awareness to hepatitis B vaccination was altogether very low (30.5%), but females (44.2%), subjects less than 40 years of age (43.5%), college graduates (34.1%), and high risk exposed personnel (57.7%) were more likely to comply compared to male subjects (odds ratio 2.53), subjects more than 40 years of age (odds ratio 3.57), non-college graduates (odds ratio 1.65), or low risk exposed (odds ratio 13.42). CONCLUSIONS: The variables considered appeared to influence awareness to vaccination. Owing to low awareness, an information campaign was started and 90% of the invited subjects were immunized.

Adult↗
PubMed2003

[Prognostic significance of the molecular markers in human gastrointestinal cancer].

Matrix metalloproteinases have been implicated in tumor progression. Matrilysin is one of the matrix metalloproteinases and is frequently overexpressed in gastrointestinal cancers. The aim of this study was to assess the validity of matrilysin as a prognostic marker of colorectal cancers. Matrilysin expression was immunohistochemically analyzed using formalin-fixed, paraffin-embedded specimens from 113 colorectal cancer patients who had undergone curative surgery. The lumenal surface of neoplastic glands in the superficial layer was apically stained, while the cytoplasm of cancer cells at the invasive front was diffusely stained for matrilysin. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 47(42%) cases, were judged as being positive for matrilysin. Matrilysin positivity was significantly correlated with the depth of invasion, lymph node metastasis, lymphatic invasion, advanced Dukes' stage, and poor outcome. Patients with matrilysin-positive cancer had a significantly shorter overall survival time than those with matrilysin-negative cancer. For patients with intermediate invasive tumor(T2 or T3), only matrilysin was a significant prognostic variable for predicting overall survival in multivariate analysis. Matrilysin expression at the invasive front could be an important marker, predicting an unfavorable prognosis after surgical treatment in patients with colorectal cancer.

Biomarkers, Tumor↗
PubMed1997

Prognostic factors in colorectal carcinomas.

Colorectal carcinoma remains a leading cause of cancer morbidity and mortality. Various clinical signs and pathologic factors have been shown to have a bearing on a patient's prognosis. Some of these factors, such as extent of disease (stage) and histologic grade, are generally accepted, while others, primarily biologic and molecular markers, have been proposed recently and remain controversial. The authors describe both more established and newly proposed variables, reviewing multivariate analyses to examine their relative importance. The recommendations of the Association of Directors of Anatomic and Surgical Pathology for the reporting of colorectal carcinomas are presented.

Biomarkers, Tumor↗
PubMed1995

CYP1A1 messenger RNA levels in placental tissue as a biomarker of environmental exposure.

The human CYP1A1 gene codes for an inducible enzyme system involved in biotransformation of certain xenobiotics, including polycyclic aromatic hydrocarbons; some of the metabolites are carcinogenic and mutagenic. Effects of environmental exposures (smoking, air pollution, and diet) on CYP1A1 gene induction in placental tissue and the modulation of induction by the CYP1A1 MspI RFLP were evaluated in two groups from Poland: 70 mother-child pairs from Krakow, a city with elevated air pollution; and 90 pairs from Limanowa, a less polluted area. Compared to placentas from nonsmoking women, CYP1A1 mRNA levels were significantly increased in placentas from current smokers (P < 0.001). Ex-smokers also had significantly higher placental mRNA levels, including women who quit smoking prior to pregnancy (P < 0.01). A marginal increase in CYP1A1 mRNA with environmental tobacco smoke exposure was evident. Within Krakow, there was an increase in CYP1A1 mRNA with ambient pollution at the place of residence for each woman, which was significant among women who were not employed away from the home (P < 0.05 controlling for smoking status, diet, and use of coal for heating). Significant increases in mRNA were associated with dietary consumption of smoked meat, cheese, and fish (P < 0.01). The CYP1A1 MspI RFLP was not a significant determinant of CYP1A1 mRNA levels after controlling for smoking and other variables. Human placenta provides a readily available and responsive system that can serve as a model for evaluating environmental and genetic determinants of CYP1A1 induction.

Adult↗
PubMed2006

Patterns of p73 N-terminal isoform expression and p53 status have prognostic value in gynecological cancers.

The goal of this study was to determine whether patterns of expression profiles of p73 isoforms and of p53 mutational status are useful combinatorial biomarkers for predicting outcome in a gynecological cancer cohort. This is the first such study using matched tumor/normal tissue pairs from each patient. The median follow-up was over two years. The expression of all 5 N-terminal isoforms (TAp73, DeltaNp73, DeltaN'p73, Ex2p73 and Ex2/3p73) was measured by real-time RT-PCR and p53 status was analyzed by immunohistochemistry. TAp73, DeltaNp73 and DeltaN'p73 were significantly upregulated in tumors. Surprisingly, their range of overexpression was age-dependent, with the highest differences delta (tumor-normal) in the youngest age group. Correction of this age effect was important in further survival correlations. We used all 6 variables (five p73 isoform levels plus p53 status) as input into a principal component analysis with Varimax rotation (VrPCA) to filter out noise from non-disease related individual variability of p73 levels. Rationally selected and individually weighted principal components from each patient were then used to train a support vector machine (SVM) algorithm to predict clinical outcome. This SVM algorithm was able to predict correct outcome in 30 of the 35 patients. We use here a mathematical tool for pattern recognition that has been commonly used in e.g. microarray data mining and apply it for the first time in a prognostic model. We find that PCA/SVM is able to test a clinical hypothesis with robust statistics and show that p73 expression profiles and p53 status are useful prognostic biomarkers that differentiate patients with good vs. poor prognosis with gynecological cancers.

Age Factors↗
PubMed2006

Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage.

This study evaluated the utility of human blood micronucleated reticulocyte (MNCD71+) frequency measurement as a cytogenetic damage biomarker. The analytical methodology was flow cytometry in conjunction with a previously described three color fluorescence labeling technique that includes anti-CD71 to focus analyses on the most immature fraction of reticulocytes [S.D. Dertinger, K. Camphausen, J.T. MacGregor, M.E. Bishop, D.K. Torous, S. Avlasevich, et al., Three-color labeling method for flow cytometric measurement of cytogenetic damage in rodent and human blood, Environ. Mol. Mutagen. 44 (2004) 427-435]. Blood specimens from 50 self-reported healthy adult volunteers were studied. In addition to MNCD71+ measurements, blood plasma folate and B12 levels were assessed, since these variables tend to influence other indices of cytogenetic damage. Time-course data are also provided for 10 cancer patients undergoing treatment. For these subjects, frequency of MNCD71+ was measured immediately before therapy, and daily during the first week of chemotherapy and/or fractionated radiotherapy. For the group of healthy volunteers, the variables of age, and folate and B12 levels demonstrated no significant effect on MNCD71+ frequency. In addition, no difference was observed between pre-treatment MNCD71+ values for cancer patients compared with healthy volunteers. Regarding chemotherapy and/or partial body radiotherapy, elevated frequencies were observed upon initiation of treatment for 9 of the 10 patients studied. Maximal effects were observed 3-5 days following initiation of therapy. The largest increases in frequency of MNCD71+ (up to 25.9-fold) were observed in those patients exposed to anti-neoplastic drugs, presumably due to the systemic red marrow exposure provided by these agents. Taken together, these data support the hypothesis that the MNCD71+ endpoint represents a valuable biomarker of cytogenetic damage that does not require cell culture or microscopy-based scoring.

Adult↗
PubMed1997

Molecular profile of advanced-stage transitional cell carcinoma of the ovary.

OBJECTIVES: Our purpose was to determine the molecular profile of advanced-stage transitional cell carcinoma in terms of immunostaining for p53, epidermal growth factor receptor and HER-2/neu, deoxyribonucleic acid index, and S-phase fraction and to analyze the prognostic significance of these markers. STUDY DESIGN: Archival paraffin-embedded tissue blocks from 29 advanced stage transitional cell carcinomas were obtained. Selected sections of the primary tumors were immunostained for p53, epidermal growth factor receptor, and HER-2/neu; deoxyribonucleic acid ploidy and S-phase fraction were determined with use of flow cytometry. Clinical information was abstracted from the medical records. Survival times were analyzed according to the life-table methods of Kaplan and Meier, and the statistical significance of the various factors was tested with the log-rank test. The proportional hazards model of Cox was used to identify prognostic factors. RESULTS: Positive immunostaining was observed for p53 in 13 cases (45%), for epidermal growth factor receptor in 14 cases (50%), and for HER-2/neu in 19 cases (65%). Tumors were diploid in 16 cases (55%) and aneuploid in 13 (45%). The S-phase fraction was < or = 15% (mean) in 13 cases (45%) and > 15% in 16 cases (55%). The median survival for the entire group was 52 months. None of the above variables had a significant effect on survival time. CONCLUSION: Neither immunostaining for p53, epidermal growth factor receptor, and HER-2/neu nor deoxyribonucleic acid ploidy nor S-phase fraction allowed us to distinguish transitional cell carcinoma from other more common epithelial ovarian cancers. In addition, no prognostic significance was associated with these biomarkers. A study of larger numbers of cases may be more elucidative.

Adult↗
PubMed2003

The role of therapeutic antibodies in drug discovery.

The last 5 years have seen a major upturn in the fortune of therapeutic monoclonal antibodies (mAbs), with nine mAbs approved for clinical use during this period and more than 70 now in clinical trials beyond phase II. Sales are expected to reach $4 billion per annum worldwide in 2002 and $15 billion by 2010. This success can be related to the engineering of mouse mAbs into mouse/human chimaeric antibodies or humanized antibodies, which have had a major effect on immunogenicity, effector function and half-life. The issue of repeated antibody dosing at high levels with limited toxicity was essential for successful clinical applications. Emerging technologies (phage display, human antibody-engineered mice) have created a vast range of novel, antibody-based therapeutics, which specifically target clinical biomarkers of disease. Modified recombinant antibodies have been designed to be more cytotoxic (toxin delivery), to enhance effector functions (bivalent mAbs) and to be fused with enzymes for prodrug therapy and cancer treatment. Antibody fragments have also been engineered to retain specificity and have increased the penetrability of solid tumours (single-chain variable fragments). Radiolabelling of antibodies has now been shown to be effective for cancer imaging and targeting. This article focuses on developments in the design and clinical use of recombinant antibodies for cancer therapy.

Antibodies↗
PubMed2005

Serum leptin and pathological findings at the time of radical prostatectomy.

PURPOSE: Obesity has been associated with a higher risk of progression following radical prostatectomy (RP). Obese men have higher serum leptin, a hormone produced by adipocytes, which has also been shown to be an in vitro prostate cancer growth factor. We examined whether serum leptin correlates with advanced pathological findings at RP. MATERIALS AND METHODS: Preoperative serum from 225 men treated with RP between 1998 and 1999 was examined for serum leptin. Multivariate logistic regression analysis was used to determine whether serum leptin was predictive of extraprostatic extension (pT3a). RESULTS: Serum leptin highly correlated with body mass index (Spearman r = 0.602, p <0.001). Serum leptin was not associated with total or percent free prostate specific antigen (PSA), biopsy or prostatectomy Gleason score, age or height. On multivariate analysis with total and percent free PSA, clinical stage, age, biopsy Gleason score, body mass index, serum leptin, and height as variables considered for entry into the model, serum PSA (p = 0.009), clinical stage (p = 0.019) and serum percent free PSA (p = 0.041) were the only variables predictive of extraprostatic extension. Serum leptin was not significantly associated with pathological stage (pT3a). CONCLUSIONS: In the current study of predominantly white men with mainly low risk disease there was no statistically significant association between serum leptin and pathological stage (pT3a) at RP. In this cohort serum leptin was not a good biomarker for predicting advanced stage at RP.

Humans↗
PubMed1995

Aging and speed of behavior: possible consequences for psychological functioning.

Over 100 years of observations have established that slowness of behavior is a characteristic of becoming old, although it is now recognized that health, use of medications, and physical activity may modify the extent of the slowing. Early research indicated that there is a limited contribution to slowing by peripheral sensory-motor factors. Substantial evidence has pointed to the central nervous system as the locus of the slowing. Recent investigators have expressed divided opinions about whether there is a pervasive general slowing of behavior by the central nervous system or whether there are specific localized mechanisms. This is not unlike early disputed views of the brain as having localized or global behavioral functions: Both principles appear to be simultaneously true. Sufficient research has been conducted to indicate that there are specific factors as well as a general process associated with the slowing of behavior with advancing age. Whether such slowing is a primary or secondary cause of age differences in cognitive processes is a significant scientific issue. A marked broadening of research on aging has been accompanied by an interest in identifying both the neurophysiological correlates of slowing as well as its role in specific cognitive processes. Yet another aspect of the changing research picture is the trend to move beyond the mere use of chronological age as the sole basis for comparing performance differences. Measurement of more independent variables is suggested as part of clusters or causal complexes that will indicate sources of the changes in speed and other aspects of behavior. These causal complexes include biological indicators such as disease, physiological capacity for work, and length of life, as well as causal complexes of social factors involving such variables as education, occupation, and ethnicity. There has been considerable discussion of markers of aging. In this approach, factors found to be closely associated with advancing age are used as measures of the effectiveness of attempts to modify the course of aging, e.g. by diet, exercise, new learning, and drugs. Along with other biomarkers of aging, speed of behavior may prove to be a criterion for assessing the impact of interventions on the rate and processes of aging. As a marker of aging, speed needs further exploration that will compare the slowness observed in different subgroups of adults with a wide range of outcomes in their productivity, capacity for adaptation to life's demands, and health. The present status of information about slowness of behavior with advancing age indicates that it is one of the most reliable features of human life.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMedDate not supplied

[Apoptosis of peripheral lymphocytes of healthy donors and patients with laryngeal neoplasms after gamma-irradiation in vitro].

Apoptosis in peripheral blood lymphocytes of healthy donors and cancer patients after gamma-irradiation with different doses was studied by the flow cytometry method. Wide intra- and interindividual variabilities of the lymphocyte radiosensitivity were observed. The radiosensitivity did not depend on the subpopulation composition of the lymphocyte pool. The persons with very low and high lymphocyte radiosensitivities were found significantly more often among the cancer patients than among the healthy donors. One can suggest that this method is useful as a biomarker of future cancer risk and prognosis of radiotherapy efficiency.

Apoptosis↗