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Results for “Biomarker variability”

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PubMed2004

Quantifying fish metallothionein transcript by real time PCR for its utilization as an environmental biomarker.

The study is aimed at introducing the hepatic level of metallothionein transcript in the fish Lithognathus mormyrus as environmental biomarker, including: (a). establishing real time PCR procedure for the evaluation of metallothionein and 18S ribosomal RNA transcript levels, (b). examining the suitability of two alternate normalization factors, 18S- and total RNA, (c). partially characterizing hepatic metallothionein transcript expression--(1). in two samples of feral fish, aimed at determining within-sample variability, (2). during a 318 days depuration experiment aimed at determining basal transcript level, (3). after cadmium injection aimed at determining maximal induced level. Hepatic transcript levels of cytochrome p4501A measured in the same individuals and published elsewhere [Environ. Toxicol. Chem. 22 (2003)], were re-analysed concurrent with the metallothionein ones. 18S rRNA was chosen as normalizing agent of choice, compensating for demonstrated partial RNA degradation in part of the preparations. Minimal and maximal metallothionein transcript levels were determined, 61+/-47 and 2159+/-905 atomol/pmol 18S rRNA, respectively. Within-sample variability of the two feral fish samples, or of similarly treated experimental fish groups, expressed as percentage of the standard deviation from the average transcript level, ranged between 41% and 80%, and as low as 3.8-fold difference between pairs of feral or experimental groups was statistically significant.

Animals↗

PubMed2005

Noninvasive markers of fibrosis for longitudinal assessment of fibrosis in chronic liver disease: are they ready for prime time?

Over the past decade, there has been a renewed enthusiasm to develop noninvasive serum markers or tests to assess the presence and severity of fibrosis in chronic liver disease. Although a single marker or test has lacked the necessary accuracy to predict fibrosis, different combinations of these markers or tests have shown encouraging results. However, interlaboratory variability and inconsistent results with liver diseases of varying etiologies have made it difficult to assess the reliability of these markers in clinical practice. In this issue of the Journal, Poynard and colleagues describe the "histological" response to lamivudine in patients with chronic HBV over a 24-month period using surrogate serum biomarkers (FibroTest-ActiTest) without corroborating histological data. Investigators found improvement in fibrosis and inflammation in 85% and 91%, respectively, despite the emergence of YMDD mutation in 41.5% of patients. The higher improvement rates reported in this study should be interpreted with caution for a number of reasons including the absence of data on virological response rates, corroboratory histological data, and data on the validity of FibroTest to evaluate fibrosis in a longitudinal manner. Although FibroTest has been studied extensively by the authors of the current study, to date there are only few independent studies. In addition to significant interlaboratory variations, these studies have shown that significant fibrosis could be missed, or conversely significant fibrosis diagnosed in the absence of minimal or no fibrosis in about 15-20% of patients. We may be approaching a time when serum biomarkers may become an integral part of the assessment of patients with chronic liver disease, but published evidence suggests that these markers are not yet ready for prime time.

Biomarkers↗

PubMed2006

Transcriptional profiling of peripheral blood cells in clinical pharmacogenomic studies.

Peripheral blood represents an attractive tissue source in clinical pharmacogenomic studies, given the feasibility of its collection from patients and its potential as a sentinel tissue to monitor perturbations of physiology in many disease states. The hypothesis is that the circulating blood cells monitor the physiological state of the organism and alter their transcriptome in response to this surveillance. However, the successful implementation of transcriptional profiling of peripheral blood cells in clinical trials represents a tremendous technical challenge for several reasons, including controlling the pre-analytical variables associated with sample processing and the interpretation of gene expression signatures generated from the complex mixture of cell types in blood. Multiple approaches for identifying transcriptomes in peripheral blood cells exist and each method is associated with significant advantages and disadvantages. Nonetheless, a growing number of studies are rapidly identifying transcriptional biomarkers in peripheral blood cells that may function as biomarkers of disease, evidence of pharmacodynamic effect, or even predictors of clinical outcomes and risk of toxicity. This review highlights the major approaches employed in global transcriptional profiling of peripheral blood cells and summarizes the available literature of initial studies in the growing field of hemogenomics. The overall purpose of the review is to focus on the development and application of technologies for the use of peripheral blood cells as a sentinel or surrogate tissue to measure disease state and drug response.

Animals↗

PubMed2004

Clinical significance of soluble p53 protein in B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: p53 status and CD38 antigen are biological factors influencing response to therapy and clinical course in B-cell chronic lymphocytic leukemia (B-CLL). This study tests the hypothesis that soluble p53 alone and in association with CD38 can enucleate B-CLL subsets at worse prognosis. DESIGN AND METHODS: Wild and mutant forms of p53 protein were evaluated in 197 B-CLL patients at diagnosis or before progression by an immunoenzymatic method in plasma using an anti-p53 monoclonal antibody. CD38 expression was analyzed by a multicolor flow cytometric assay. RESULTS: Higher levels of both soluble p53 (sp53) and CD38 were significantly correlated with intermediate and high Rai stages, with higher beta2-microglobulin and soluble CD23 values, determined at diagnosis. Shorter overall survival (OS) and progression-free survival (PFS) were both observed in sp53+ and CD38+ patients (p<0.0001). Simultaneous positivity or negativity for sp53 and CD38 identified two subsets of patients, the former with a worse prognosis and the latter with a better prognosis with regard to PFS (p<0.0001) and OS (p<0.0001). The predictive value of sp53 and CD38 was retained among the patients within the intermediate Rai risk group. INTERPRETATION AND CONCLUSIONS: sp53 and CD38 together with ZAP-70 were confirmed to be independent prognostic factors in multivariate analysis. With regard to PFS, ZAP-70, sp53 and CD38 were confirmed to be independent prognostic factors. Concerning OS, ZAP-70, CD38 and age (< or > 60 years) were independent prognostic factors whereas sp53 showed only a tendency towards statistical significance.

ADP-ribosyl Cyclase 1↗

PubMed2000

Vitamin A physiology and its application as a biomarker of contaminant-related toxicity in marine mammals: a review.

In recent decades, marine mammal populations living in highly polluted areas have experienced incidences of low reproductive success, developmental abnormalities and disease outbreaks. In many of these cases, environmental contaminants were suspected as causal or contributing factors. However, demonstrating a mechanistic link between contaminant exposure and effect in marine mammal populations has proven challenging. Consequently, the development and application of relatively noninvasive biomarkers represents a potentially valuable means of monitoring wildlife populations exposed to elevated levels of contaminants. One touted biomarker is vitamin A (retinol), a "dietary hormone" whose metabolites are required for reproduction, growth, development, immune function, vision and epithelial maintenance. Laboratory studies have shown that many contaminants, including polychlorinated biphenyls (PCBs), polychlorinated dibenzo-para-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), can disrupt vitamin A physiology and alter the distribution of its essential metabolites. Field studies suggest that complex environmental mixtures of these chemicals can also interfere with vitamin A dynamics in free-ranging marine mammals and other fish-eating wildlife. However, circulatory retinol, which is the least invasive measurement of vitamin A status, appears to have variable responses to contaminant exposure. In addition, "normal" circulatory retinol levels have not yet been described for most wildlife species, and not enough is known about the natural physiological events that can alter these concentrations. Confounding factors must therefore be characterized before retinoids can be used as an effective indicator of adverse health effects in marine mammals exposed to elevated levels of environmental contaminants.

Animals↗

PubMed2006

MCA1 detection of histone H3 serine 10 phosphorylation, a novel biomarker for determination of mitotic indices.

Previously we identified circulating autoantibodies in high titre in the serum of a patient with biopsy-proven discoid lupus erythematosus reactive to serine/threonine phosphoepitopes of the novel mitotic chromosomal autoantigen we named MCA1. MCA1-reactive antibodies have subsequently been demonstrated to bind to the modified histone H3 (H3K9me3S10ph). In this study we utilised Epstein Barr virus (EBV) infection of peripheral blood mononuclear cells collected from this patient to immortalise B-lymphocytes producing MCA1-reactive antibodies. We found MCA1-reactive antibody production by the EBV-immortalised B-lymphocytes unstable in culture. We discuss the possibilities of producing MCA-1-reactive reagents through protein engineering methods (variable or complementarity-determining region grafting) and to modulate antibody affinity through library technologies (such as phage, yeast or ribosome display). Clinical studies have shown that carcinogenesis is most often linked to the development of proliferative abnormalities and proliferative activity has prognostic significance in a variety of human tumours. Here we demonstrate the potential utility of antibodies reactive to H3K9me3S10ph (MCA1), which is only detected on mitotic chromatin, as a marker for cell proliferation in FACS analysis, tissue section staining and in determination of mitotic indices.

Aged↗

PubMed2003

Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma.

PURPOSE: The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes. PATIENTS AND METHODS: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently healthy women, 141 women with benign abdominal diseases, and 146 women with histologically proven primary ovarian carcinoma. We then calculated the diagnostic sensitivity and specificity of this test and examined the association of serum hK6 concentration with various clinicopathologic variables and patient survival. RESULTS: Serum hK6 concentration between normal and benign disease patients was not different (mean, 2.9 and 3.1 micro g/L, respectively). However, hK6 in presurgical serum of ovarian cancer patients was highly elevated (mean, 6.8 micro g/L; P <.001). Serum hK6 decreased after surgery (to a mean of 3.9 micro g/L) in 68% of patients. The diagnostic sensitivity of serum hK6 at 90% and 95% specificity is 52% and 47%, respectively, in the whole patient population. For early stage disease (stage I or II), sensitivity is approximately 21% to 26%. When combined with CA-125, at 90% specificity, sensitivity increases to 72% (for all patients) and to 42% in stage I or II disease. Serum hK6 concentration correlates moderately with CA-125 and is higher in patients with late-stage, higher-grade disease and in patients with serous histotype. Preoperative serum hK6 concentration is a powerful predictor of disease-free and overall survival in both univariate and multivariate analyses. CONCLUSIONS: Serum hK6 concentration seems to be a new biomarker for ovarian carcinoma and may have value for disease diagnosis and prognosis.

Adult↗

PubMed2026

Polygenic Profiles Are Associated with Multidomain Biochemical Adaptations Across a Competitive Season in Professional Football Players: A Longitudinal Observational Study.

Background/Objectives: The physiological adaptations required to sustain elite football performance are influenced by both genetic background and dynamic biochemical responses, although their interaction across a full competitive season remains insufficiently characterized. This study aimed to examine the association between polygenic profiles and longitudinal biochemical adaptations in professional football players. Methods: Forty male professional football players competing in the Spanish league were monitored across two consecutive seasons. Blood samples were collected at six time points representing different phases of the competitive cycle. Biomarkers related to muscle metabolism, iron status, and hepatic function were analyzed. Polygenic profiles were calculated using Total Genotype Scores (TGS) for muscle performance, hepatic resilience, and metabolic efficiency. Associations were initially explored using Pearson correlations and subsequently evaluated using linear mixed-effects models accounting for repeated measurements within subjects. Results: Exploratory correlation analyses identified several associations between polygenic profiles and biochemical markers. Muscle performance TGS was inversely associated with serum iron (r = -0.36, p = 0.017) and positively associated with CK (r = 0.32, p = 0.041), Hb (r = 0.29, p = 0.046), and Hct (r = 0.33, p = 0.024). Hepatic resilience TGS showed inverse associations with ALT (r = -0.39, p = 0.012), urea (r = -0.51, p = 0.011), and BUN (r = -0.51, p = 0.011). Metabolic efficiency TGS was negatively associated with AST (r = -0.43, p = 0.044), ALT (r = -0.33, p = 0.025), and GGT across multiple time points (p = 0.001-0.013). However, although several nominal associations emerged in linear mixed-effects models accounting for repeated measurements, none remained statistically significant after false discovery rate correction. These findings should therefore be interpreted as exploratory and hypothesis-generating. Conclusions: Polygenic profiles may be associated with inter-individual variability in biochemical adaptations throughout a competitive season. These findings suggest the integration of genomic and biochemical data in precision athlete monitoring, while highlighting causal relationships and predictive applications require further investigation.

Humans↗

PubMed2000

Prognostic role of plasminogen-activator-inhibitor-1 levels in treatment with streptokinase of patients with acute myocardial infarction.

BACKGROUND: The antifibrinolytic effect of plasminogen-activator-inhibitor type 1 (PAI-1) may be responsible for delays in reperfusion and/or reinfarctions after streptokinase (STK) therapy in patients with acute myocardial infarction (AMI). HYPOTHESIS: This study aimed to demonstrate the prognostic role of pretreatment PAI-1 levels for the outcome of STK therapy in patients with AMI, depending on reperfusion and/ or reinfarction. METHODS: The mean pretreatment PAI-1 level of 104 patients with AMI, treated with STK, determined by chromogenic method, was 5.8 +/- 8.6 U/ml, range 0.3-66.2 U/ml. Streptokinase therapy was successful when reperfusion was achieved, as assessed noninvasively, without subsequent reinfarction; it failed when reperfusion was delayed and/or reinfarction developed. RESULTS: Fibrinolysis with STK failed significantly in patients with elevated pretreatment PAI-1 levels (p < 0.05), especially with levels >4.0 U/ml (p< 0.01). The mean pretreatment PAI-1 level was significantly higher in unsuccessfully treated patients. Multivariate statistical testing demonstrated that among pretreatment variables, elevated PAI-1 activity was the most significant independent risk factor of failed fibrinolysis with STK. CONCLUSIONS: Among pretreatment variables, elevated pretreatment PAI-1 activity in patients with AMI was the most significant independent risk factor of failed fibrinolysis with STK, especially at levels > 4.0 U/ml.

Adult↗

PubMed2005

Changes in the defined daily dose; CYP2D6/CYP3A metabolism as an indicator for dose-setting problems.

OBJECTIVE: Interindividual variability is common at all stages of drug absorption, distribution, pharmacodynamics, metabolism and elimination. In this study, we focused on two enzymes involved in phase-I drug metabolism as markers of pharmacological variability: the CYP3A and CYP2D6 subsystems of cytochrome P450. The main aim of our study was to determine whether substrate drugs for CYP2D6 and/or CYP3A enzymes, showing high interindividual matabolic variability, are more prone to postmarketing adjustments of defined daily dose (DDD). METHODS: A case-control design was used. We identified all DDD changes between 1982 and May 2004 through the website of the WHO Collaborating Centre for Drug Statistics Methodology. Cases were drugs with a DDD change and controls were other drugs with unchanged DDDs. Information about metabolism pathway, introduction year, literature exposure and administration route was retrieved. RESULTS: We included 88 cases and 176 controls. Of the 88 cases, 51 were dosage decreases (58.0%). Overall, DDD changes were not associated with CYP2D6/CYP3A metabolism (OR 1.92; 95%CI 0.78-4.72). However, DDD decreases were associated with CYP2D6/CYP3A metabolism (OR 3.21; 95%CI 1.25-8.26). Adjusting for introduction year weakened this effect (OR 2.78; 95%CI 0.98-7.90). CONCLUSION: Our study indicates that CYP2D6 and CYP3A substrates are more likely to require a DDD decrease after granting of market authorisation. However, this effect was diminished by adjusting for period of introduction. The implication of this finding is that variability indicators, as is demonstrated in this study for CYP2D6/CYP3A metabolism, can exert their influence on a wide variety of drug measures, such as the DDD.

Biomarkers↗

PubMed1989

RECPAM: a computer program for recursive partition amalgamation for censored survival data and other situations frequently occurring in biostatistics. II. Applications to data on small cell carcinoma of the lung (SCCL).

The RECPAM methodology previously presented in part I (A. Ciampi et al., Comput. Methods Programs Biomed. 26 (1988) 239-256) is applied to the analysis of survival data on small cell carcinoma of the lung (SCCL). It is shown how RECPAM can help answer the following questions which occur frequently in the analysis of clinical data: Is it possible to find a classification of patients with a certain disease into distinct prognostic groups? Given a covariate of special interest, does it have an independent prognostic significance even after confounding is taken into account? Does the prognostic significance of a covariate of special interest vary across patient subgroups? For the SCCL data, a prognostic classification is obtained and the tumor marker LDH is treated as a variable of special interest. Many features of RECPAM are illustrated, including, among others, Forward and Backward (Pruning) Stopping Rules, treatment of missing data, and use of several dissimilarity measures.

Biomarkers, Tumor↗

PubMed2001

Utility of cardiac troponin measurement after cardiac surgery.

Postoperative cardiac failure due to myocardial necrosis remains a major complication in cardiac surgical procedures and its diagnosis is still difficult. In fact, cardiac enzymes, electrocardiogram and echographic signs are often misleading. The prognostic valve of troponin I after coronary artery bypass or conventional value surgery has been evaluated in 500 adult patients. Postoperative troponin I concentrations after cardiac surgery represent an independent variable associated with mortality (in-hospital death) and morbidity (low cardiac output and acute renal failure).

Biomarkers↗

PubMed2000

Immunohistochemical markers for intracranial ependymoma recurrence. An analysis of 88 cases.

Intracranial ependymomas are the third most common primary brain tumor in children. Although clinical and histological criteria for ependymoma prognosis are recognized, studies have reported contradictory results. Prognostic significance based on immunohistochemistry of ependymomas has been reported in a few studies. Eighty-eight patients with intracranial ependymomas were examined retrospectively for immunoexpression of various tumor-associated antigens and apoptosis. The results demonstrated significant preponderance of expression of the tenascin, vascular endothelial growth factor protein (VEGF), epidermal growth factor (EGFR), and p53 protein in high-grade tumors. Also high-grade ependymomas revealed more prominent labeling indices (LI) for proliferative marker Ki-S1 and lower LI for cyclin-dependent kinase inhibitor p27/Kip1. For low-grade ependymomas the progression free survival time (PFS) was found to be significantly shorter for Ki-S1 LI>/=5%, and for tenascin, VEGF, and EGFR positivity. For high-grade ependymomas PFS was found to be significantly reduced for age <16 years, subtotal tumor removal, p27 LI <20%, p53 positivity, and for apoptotic index (AI) <1%. The classification regression tree analysis exhibited four groups of ependymomas; (1) low-grade tenascin negative (32 cases, recurrence rate=0), (2) high-grade with AI >/=1% (21 cases, recurrence rate=57%), (3) low-grade tenascin-positive (10 cases, recurrence rate=89%), and (4) high-grade with AI <1% (25 cases, recurrence rate=100%). So, the immunohistochemical variables were found to be strongest predictors of ependymoma recurrence and they seem to be useful for assessing individual tumor prognosis in routinely processed biopsy specimen.

Adolescent↗

PubMed1997

Lymphocytes with cerebriform nuclei in chronic B-cell lymphoproliferative diseases.

Two patients with chronic lymphoproliferative diseases, a splenic marginal zone lymphoma and hairy cell leukaemia variant, were reported. In both diseases a B-immunophenotype was demonstrated but a variable percentage of lymphoid cells (30 and 52%) showed a highly irregular nuclear outline, sometimes mimicking the nuclei of Sézary cells.

Aged↗

PubMed2000

Increased morbidity and high variability of cyclosporine levels in pediatric heart transplant recipients.

OBJECTIVES: This study analyzed the relationship of variability in routine trough cyclosporine (CSA) levels to morbidity after pediatric cardiac transplantation. BACKGROUND: Due to high interindividual variation between dosage and blood concentrations, trough surveillance CSA levels are routinely performed after cardiac transplantation to adjust dosages. In addition, trough CSA levels have been used as a measure of patient compliance in transplant recipients. Recent investigations have demonstrated a relationship between late rejection and mistimed CSA dosing intervals, which could also lead to CSA levels that are incorrectly presumed to be trough levels. METHODS: Trough surveillance whole-blood CSA levels were retrospectively reviewed in 49 pediatric heart transplant recipients who had a median follow-up of 42 months (range 6 to 138 months). All patients received the same immunosuppression regimen (CSA, azathioprine, and steroids), the same CSA-level surveillance protocol, and the same stabilization of CSA dose and level in the therapeutic range (150 to 300 ng/ml) prior to hospital discharge. CSA levels drawn because of coexisting phenomena (drug interaction, gastroenteritis) that could cause CSA-level fluctuation were excluded from analysis. Cyclosporine variability was measured as the percentage of CSA levels that were considered sub-therapeutic (< or = 100 ng/ml), toxic (> or = 450 ng/ml), or both. Cyclosporine-level variability was then analyzed in respect to demographic and outcome variables. RESULTS: For the group, the median percentage of sub-therapeutic levels was 3% (range, 0% to 16%); the median percentage of toxic levels was 5% (range, 0% to 36%); the median of the combination of sub-therapeutic and toxic levels was 10% (0% to 38%). Eight of the 49 patients (16%) has a high (>20%) percentage of sub-therapeutic + toxic levels or high CSA variability. High CSA variability was significantly associated with recipients > 12 months of age (p = 0.028), and recipients with a history of non-compliance (p < 0.001). Patients with high CSA variability had a significantly higher median number of hospitalized days per year of follow-up (p = 0.036), higher rate of recurrent rejection (> or = 2 episodes; p = 0.0003), and higher death rate more than 6 months after transplant (p = 0.01). CONCLUSIONS: Although this study could not determine cause, high variability in trough CSA levels was a marker for pediatric heart transplant recipients at greater risk for recurrent rejection and hospitalization after transplantation.

Adolescent↗

PubMed2000

Consumption of black and green tea had no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals.

OBJECTIVE: Firstly, to study the effect of tea and tea polyphenols on cardiovascular risk indicators of the inflammatory system (IL6, IL1beta and TNF-alpha, CRP), and on haemostasis and endothelial proteins with an acute phase behaviour (fibrinogen, vWF, PAI-1, FVIIa and u-PA). Secondly, to study the relationship between plasma levels of antioxidants (alpha-tocopherol, beta-carotene and vitamin C) and these acute-phase, cardiovascular risk indicators. DESIGN: Randomized study. SUBJECTS: Sixty-four smoking healthy volunteers were recruited by newspaper advertisements; there were five dropouts. INTERVENTION: Four-week administration of black tea, green tea, green tea polyphenol isolate and mineral water ( 13-16 per group). MEASURES: Plasma levels of the inflammatory markers IL6, IL1beta, TNF-alpha, CRP, fibrinogen, vWF, PAI-1, FVIIa and u-PA and of the antioxidants alpha-tocopherol, beta-carotene and vitamin C. RESULTS: Different dosages of tea polyphenols had no effect on inflammation, haemostasis and endothelial markers. There was a significant negative correlation between the levels of the antioxidant beta-carotene and the inflammation markers IL6 and fibrinogen (r = -0.35 and r = -0.37, respectively, P<0.01) in this group of smokers. Remarkably, there was a significant positive correlation between the levels of the antioxidant alpha-tocopherol and the inflammation marker IL6 (r = 0.28, P<0.05). CONCLUSIONS: Tea drinking had no effect on the levels of the inflammation, haemostasis and endothelial cardiovascular risk factors measured. We did observe a relationship between the antioxidant variables alpha-tocopherol and beta-carotene and inflammation markers in this group of healthy smoking subjects.

Acute-Phase Reaction↗

PubMed2000

Urea as a marker of adequacy in hemodialysis: lesson from in vivo urea dynamics monitoring.

BACKGROUND: "Dialysis dose," a concept developed by Sargent and Gotch based on urea kinetic modeling, is a useful and recognized tool that is used to quantitate and optimize a dialysis-efficacy program. However, it has been shown that oversimplification of the "dialysis adequacy" concept to the Kt/V index might lead to dramatic underdialysis and subsequent deleterious consequences on morbidity and mortality of dialysis patients. With this perspective, the determination of Kt/V must be very cautious and rely on accurate measurement of postdialysis urea concentration and its use integrated as a tool in a quality-assurance process. METHODS: In this study, we analyzed urea dynamics by means of a blood side (ultrafiltrate) continuous online urea monitoring system interfaced with a two-pool model hosted in a microcomputer. The study was designed to provide instantaneous dialysis performances (body and dialyzer clearances, dialyzer mass transfer coefficient) and to determine the in vivo functional permeability characteristics of the patient [intercompartment urea mass transfer coefficient (Kc)]. Thirteen end-stage renal disease patients (age 54 +/- 16 years; 12 male and 1 female) were studied during nine consecutive dialysis sessions (3 weeks). RESULTS: Urea kinetics obtained from the urea monitoring system fitted closely the urea kinetic modeling prediction, confirming the validity of the double-pool model structure. Effective in vivo urea mass transfer coefficient averaged 912 +/- 235 mL/min/1.73 m2, a value close to those reported with more invasive methods. Large variations ranging from 363 to 1249 mL/min were observed among patients, confirming very large interindividual patient permeability differences. Interestingly, the urea mass transfer coefficient was inversely correlated with the postdialysis rebound values. Intraindividual variations were also noted as a function of time denoting functional changes in urea mass transfer coefficient values. The urea distribution volume was 38.1 +/- 7, 8 L (53 +/- 8% body weight). V1 referring to the extracellular volume and V2 to the intracellular volume were 9 +/- 2 L (13 +/- 2% body weight) and 29.2 +/- 6.6 L (41 +/- 1.3% body wt), respectively. The extracellular/intracellular volume ratio was 0.31 (approximately one third) and was not as usually defined by the paradigm 1/2 ratio. CONCLUSION: Online double-pool urea kinetic modeling gave a new insight in urea kinetic modeling approach. Urea dynamics fit perfectly a double-compartment model structure. Accessible extracellular volume to hemodialysis is smaller than expected. The in vivo urea mass transfer coefficient must be considered as an individual and variable characteristic of ESRD patients that should be taken into consideration when prescribing the hemodialysis schedule.

Adult↗

PubMed1998

Relations of nm23 expression to clinicopathologic variables and proliferative activity of gastric cancer lesions.

Relationships of nm23 expression and 12 clinicopathologic variables and proliferative activity of cancer cells were examined in 55 gastric cancer patients to clarify the effects of nm23 expression on the factors and activity in gastric cancer. Expression of nm23 was determined by immunohistochemically stained sections using a monoclonal antibody, nm23H-1. Proliferative activity was immunohistochemically evaluated by proliferating cell nuclear antigen (PCNA) labeling index (LI) using a monoclonal antibody PC10. Expression of nm23 was found in 24 lesions (positive group) but not in 31 lesions (negative group). With regard to clinicopathologic variables, a significant (p < 0.05) difference between the positive and negative groups was found in 1 of the 12 factors, depth of cancer invasion. PCNA LI (48.9 +/- 11.6%) of the former group was significantly (p < 0.05) higher than that (40.3 +/- 12.6%) ot the latter, although multiple regression analysis showed that nm23 expression was not one of the most influencing variables for PCNA LI. The results may suggest that expression of nm23 in gastric cancer lesions is correlated to tumor progression and/or proliferation rather than suppression of metastasis.

Aged↗