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PubMedDate not supplied

[Biochemical markers of bone remodeling: pre-analytical variations and guidelines for their use. SFBC (Société Française de Biologie Clinique) Work Group. Biochemical markers of bone remodeling].

Biochemical markers of bone turnover have been developed over the past 20 years that are more specific for bone tissue than conventional ones such as total alkaline phosphatase and urinary hydroxyproline. They have been widely used in clinical research and in clinical trials of new therapies as secondary end points of treatment efficacy. Most of the interest has been devoted to their use in postmenopausal osteoporosis, a condition characterized by subtle modifications of bone metabolism that cannot be detected readily by conventional markers of bone turnover. Although several recent studies have suggested that biochemical markers may be used for the management of the individual patient in routine clinical practice, this has not been clearly defined and is a matter of debate. Because of the crucial importance to clarify this issue, the Société Francaise de Biologie Clinique prompted an expert committee to summarize the available data and to make recommendations. The following paper includes a review on the biochemical and analytical aspects of the markers of bone formation and resorption and on the sources of variability such as sex, age, menstrual cycle, pregnancy and lactation, physical activity, seasonal variation and effects of diseases and treatments. We will also describe the effects of pre-analytical factors on the measurements of the different markers. Finally based on that review, we will make practical recommendations for the use of these markers in order to minimize the variability of the measurements and improve the clinical interpretation of the data.

Adolescent↗
PubMedDate not supplied

Reduction of night/day difference in melatonin blood levels as a possible disease-related index in schizophrenia.

OBJECTIVE: Aim of this study was to verify if a simple index as night-day plasma MLT level variation is able to confirm the existing data on circadian melatonin alterations in schizophrenia and if a relationship to disease itself instead of the actual clinical state can be suggested. SETTING AND DESIGN: Ten consecutively admitted male schizophrenic inpatients were examined. METHODS: The blood samples for melatonin were collected at 3.00 a.m. and 15.00 p.m. and consequently calculated the values of Delta () (MLT h.3.00- MLT h.15.00). We divided the sample into two subgroups: < 30 pg/ml and > 30 pg/ml taking 30 pg/ml as an arbitrary value, based on literature data, that should indicate a physiologically correct value of. RESULTS: The 70% of the sample was under the 30 pg/ml value of (13.61 +/- 4.0) or was lacking of the characteristic circadian pattern of MLT secretion, whilst the 30% of the sample was over the 30 pg/ml value of (83.60 +/- 16.34) or was in presence of the characteristic circadian pattern of MLT secretion (p=.0001). No correlation was found between values and the scale and subscales scores for the assessment of psychopathology. MAIN FINDINGS: The data confirm the lack of the characteristic circadian pattern of MLT secretion in schizophrenics. CONCLUSION: The absence of significant correlation between night / day melatonin level differences and actual psychopathology variables should indicate that the suppression of is mostly related to the disease and independent from the clinical state. A neuroleptic-treatment effect cannot be excluded so far.

Adult↗
PubMed1998

A cross sectional analysis of 5 different markers of collagen degradation in rheumatoid arthritis.

OBJECTIVE: To compare 5 different assays measuring collagen degradation in rheumatoid arthritis (RA). METHODS: Daily serum samples and 3 consecutive 24 h urine samples were obtained from 25 patients with RA and 20 control subjects. Levels of pyridinoline (PYD), deoxypyridinoline (DPYD), n-telopeptide (NTx), CrossLaps (XL), and carboxy-terminal peptide of type I collagen (ICTP) were determined by ELISA or radioimmunoassay. PYD, DPYD, NTx, and XL were measured in urine and expressed as a ratio of the amount of crosslink to mmoles of creatinine (Cr). ICTP was determined in serum. The day-to-day variability of urinary collagen crosslink levels and serum ICTP was assessed over 3 day hospitalization. RESULTS: Four of the 5 markers were significantly elevated in the RA cohort compared to controls: PYD (nmol)/Cr (median 33.8 vs 19.3; p = 0.0001), NTx (nmol)/Cr (median 22.5 vs 13.8; p = 0.01), XL (microg)/Cr (median 191.4 vs 126.1; p = 0.01), and ICTP (microg/l) (median 5.8 vs 3.7; p = 0.001). In the RA group, higher levels of the markers were associated with concomitant prednisone therapy. The levels of the 4 urine markers and of ICTP in serum exhibited little day-to-day variability. CONCLUSION: Biochemical evidence of increased collagen degradation can be readily observed in RA using simple quantitative assays. These measures have minimal short term, day-to-day variability and hence may be useful to assess the effect of potentially disease modifying therapies.

Amino Acids↗
PubMed2026

Prognostic value of the lactate-to-albumin ratio in adult sepsis: An updated systematic review of prognostic evidence.

BACKGROUND: The lactate-to-albumin ratio (LAR) has emerged as a potential prognostic biomarker in sepsis. This systematic review evaluated the prognostic value of LAR for mortality in adults with sepsis or septic shock. METHODS: PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library were searched from inception through March 2026. Studies evaluating mortality-related prognostic performance of LAR in adults with sepsis or septic shock were included. Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool. Adjusted odds ratios (ORs) and hazard ratios (HRs) were evaluated separately because of methodological heterogeneity. Discrimination was assessed using study-specific area under the curve (AUC), sensitivity, specificity, and LAR thresholds. RESULTS: Fourteen primary studies were included. Higher LAR was consistently associated with increased mortality across emergency department and intensive care populations. AUC values generally ranged from approximately 0.65 to 0.87, although one smaller cohort reported an AUC of 0.976. Several multivariable analyses demonstrated associations between higher LAR and mortality after adjustment for clinical covariates. Adjusted ORs and HRs were not pooled because of differences in LAR scaling, thresholds, mortality endpoints, and adjustment strategies. Considerable variability was observed in reported cut-offs and diagnostic performance. CONCLUSIONS: Higher LAR is associated with mortality in adult sepsis and may provide complementary prognostic information. However, clinical and methodological heterogeneity precludes a universal cut-off or single pooled adjusted effect. Standardized prospective multicenter studies are required before routine clinical implementation.

Humans↗
PubMed2000

Statistical models for analysis of cytogenetic biomarkers.

BACKGROUND: Bleomycin-induced chromosomal breaks (CB) and sister chromatid exchange (SCE) in peripheral blood lymphocytes have been shown to be sensitive cytological markers for susceptibility to DNA damage in patients with various types of cancer and in healthy controls. Factors such as age, sex, smoking, and alcohol consumption could affect the values of some of these biomarkers and should be considered as covariates when analyzing cytogenetic biomarkers because these factors can affect the frequency of CB and SCE. METHODS: We propose a statistical method using negative binomial (NB) distribution to evaluate the numbers of CB and SCE. In order to determine the best model to represent the frequency of CB and SCE, we compared the NB model with the widely used Poisson model and log-transformed normal model by using generalized linear models. To demonstrate the better fit of the NB model, we analyzed three different data sets from studies conducted at The University of Texas M.D. Anderson Cancer Center. The first set was a case-control study of lung cancer in a population of African Americans and Mexican Americans (286 cases and 156 controls), the second set consisted of 311 head and neck cancer patients, and the third set consisted of 105 Hodgkin's disease patients. RESULTS: For CB; the estimates of the variability for Hodgkin's disease, head and neck, and lung cancers were 487.24, 502.82, and 520.15, respectively. For SCE, the estimates of the variability for Hodgkin's disease was 9777.01. For CB, the dispersion estimates under the three models (Poisson, NB, and Normal) for Hodgkin's disease, head and neck, and lung cancers were: 12.30, 1.20, 0.85; 8.94, 1.05, 0.22; and 10.10, 1.05, 0.25, respectively. For SCE (Hodgkin's disease only), the dispersion estimates under the three models (Poisson, NB, and Normal) were 30.91, 1.11, 0.10, respectively. CONCLUSIONS: Our results demonstrate that the NB model provides a better interpretation and fit for the frequency of CB and SCE in different cancer types. Therefore, we recommend it as a model for the analysis of cytogenetic biomarkers.

Biomarkers↗
PubMed2002

Urinary 1-hydroxypyrene as a biomarker of internal dose of polycyclic aromatic hydrocarbons in carbon black workers.

In this study, a total of 30 workers were selected, including eight wet pelletizing workers and 22 packaging workers. For all selected workers, urine samples were collected on the first day pre-shift, first day post-shift and fifth day post-shift, and their urinary 1-hydroxylpyrene levels (1-OHP) were determined (denoted as BM1pre, BM1post and BM5post, respectively). Personal respiratory exposures, including both inhalable particle-bound PAHs (Cinh) and gaseous PAHs (Cgas), together with dermal exposure to particle-bound PAHs (Cskin) were measured. Personal background information, including age, sex and smoking habit, was carefully registered. Pyrene exposure was statistically significantly correlated with exposure to PAHs and carcinogenic PAHs. Multiple linear regression analysis results showed that the BM1post values could not be explained by workers' exposures. For BM5post in packaging workers, both the regression model (R2 = 0.73) and the regression coefficients for Cgas, Cinh and Cskin were statistically significant (P < 0.05). For pelletizing workers, the R2 value was higher but was not statistically significant because of the smaller number of workers. The resultant regression coefficients for 'sex', 'smoking habit' and 'age' were statistically insignificant (P >> 0.05), which could be because these variables made relatively small contributions to BM5post. In conclusion, this study suggests BM5post could be a suitable indicator for PAH exposures of carbon black workers, on the condition that both respiratory (including gaseous PAHs and particle-bound PAHs) and dermal exposures have been assessed.

Adult↗
PubMed2006

Oxidative stress in pterygium: relationship between p53 and 8-hydroxydeoxyguanosine.

PURPOSE: Ultraviolet (UV) radiation is known to cause oxidative DNA damage and is thought to be a major factor implicated in the pathogenesis of pterygium, a benign invasive lesion of the bulbar conjunctiva. Among all the photooxidative DNA products, 8-hydroxydeoxyguanosine (8-OHdG) is regarded as a sensitive and stable biomarker for evaluating the degree of DNA damage. The protein p53 is a major cell stress regulator that acts to integrate signals from a wide range of cellular stresses. UV radiation can cause mutations in the p53 tumor suppressor gene that, when inactivated through mutation and loss of heterozygosity, can lead to cell proliferation and genomic instability. In many types of UV-radiation damaged cells, p53 is overexpressed and immunohistochemically detectable. Recent data on tissues exposed to factors inducing oxidative stress have provided evidence of the concomitant presence of increased levels of 8-OHdG and protein p53. To verify a possible significant association between p53 and 8-OHdG, we examined a series of 31 Ecuadorian pterygia for the expression of the two markers. Moreover, we evaluated if clinical variables such as patient's age, gender, geographic location, and disease stage, might play a role affecting the 8-OHdG and p53 immunohistochemical staining results. METHODS: Primary pterygium samples were treated for immunohistochemical evaluations of 8-OHdG and p53 protein. Mouse monoclonal antibodies to 8-OHdG and p53 were used. Statistical analyses were performed using the SPSS 12 statistical software package. RESULTS: In our study, 21 (67.74%) pterygial samples were positive for 8-OHdG staining, 11 (35.48%) specimens were positive for p53 expression, and all negative control samples showed no staining. The staining for 8-OHdG was limited to the nuclei of the epithelial layer. No substantial staining was visible in the subepithelial fibrovascular layers. No differences in the pattern of staining between 8-OHdG and p53 were observed. All samples positive for p53 (11/31, 35.48%) were also positive for 8-OHdG immunostaining, and all specimens negative for 8-OHdG (10/31, 32.26%) were also negative for p53. When analyzed by Fisher's exact test, 8-OHdG expression was significantly associated with p53 positivity (p=0.0049). Student's t-test demonstrated statistically significant association between the expression of p53 and age (p=0.02). The correlation between the two markers and the other clinical variables revealed no statistically significant association. CONCLUSIONS: Although pterygium is a lesion with limited local invasion and an inability to metastasize, the concomitant presence of altered p53 in 8-OHdG-immunoreactive cells could provide evidence of apparent genetic instability, which is in contrast to its benign clinical course.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Site-specific data confirm arsenic exposure predicted by the U.S. Environmental Protection Agency.

The EPA uses an exposure assessment model to estimate daily intake to chemicals of potential concern. At the Anaconda Superfund site in Montana, the EPA exposure assessment model was used to predict total and speciated urinary arsenic concentrations. Predicted concentrations were then compared to concentrations measured in children living near the site. When site-specific information on concentrations of arsenic in soil, interior dust, and diet, site-specific ingestion rates, and arsenic absorption rates were used, measured and predicted urinary arsenic concentrations were in reasonable agreement. The central tendency exposure assessment model successfully described the measured urinary arsenic concentration for the majority of children at the site. The reasonable maximum exposure assessment model successfully identified the uppermost exposed population. While the agreement between measured and predicted urinary arsenic is good, it is not exact. The variables that were identified which influenced agreement included soil and dust sample collection methodology, daily urinary volume, soil ingestion rate, and the ability to define the exposure unit. The concentration of arsenic in food affected agreement between measured and predicted total urinary arsenic, but was not considered when comparing measured and predicted speciated urinary arsenic. Speciated urinary arsenic is the recommended biomarker for recent inorganic arsenic exposure. By using site-specific data in the exposure assessment model, predicted risks from exposure to arsenic were less than predicted risks would have been if the EPA's default values had been used in the exposure assessment model. This difference resulted in reduced magnitude and cost of remediation while still protecting human health.

Algorithms↗
PubMed2006

A pilot pharmacokinetic and antiangiogenic biomarker study of celecoxib and low-dose metronomic vinblastine or cyclophosphamide in pediatric recurrent solid tumors.

Tumor vasculature is a reasonable target for cancer therapy and lower more frequent doses of traditional chemotherapeutics [low-dose metronomic (LDM) chemotherapy] has been shown to have antiangiogenic efficacy. This study evaluated the safety and pharmacokinetics of celecoxib and LDM vinblastine or cyclophosphamide in children with recurrent, refractory solid tumors. We also investigated whether a subset of circulating plasma proteins are surrogate markers of angiogenic activity. Thirty-three children were enrolled in this pilot study and received celecoxib (250 mg/m(2) PO b.i.d.) and either vinblastine (1 mg/m(2) IV 3 x /wk) or cyclophosphamide (30 mg/m(2) PO daily) continually. Celecoxib alone and with LDM chemotherapy was well tolerated and plasma concentrations were consistent with those shown to have antiangiogenic activity. Four patients (13%) had durable stable disease (28 to 78 wk) although no complete or partial responses were observed. The surrogate markers measured (vascular endothelial growth factor, basic fibroblast growth factor, soluble vascular cell adhesion molecule, soluble intercellular cell adhesion molecule, endostatin, and thrombospondin-1) were highly variable and no statistically significant relationship between them and disease progression or maintenance of stable disease was observed. We concluded that this regimen is well tolerated hence supporting the use of this form of therapy in pediatric patients. However, future studies should include more homogenous patient populations and focus on validating surrogate markers to monitor treatment activity.

Adolescent↗
PubMed2003

Plasma and cerebrospinal fluid alpha1-antichymotrypsin levels in Alzheimer's disease: correlation with cognitive impairment.

alpha-1-Antichymotrypsin (ACT) is present in neuritic plaques in which it participates in the inflammatory cascade of Alzheimer's disease (AD). Reports of blood ACT levels in AD, and its usefulness as a disease biomarker, have been conflicting. In an effort to clarify this, we measured plasma ACT levels in 516 white subjects including 359 subjects with probable or possible AD, 44 subjects with other late-life dementias, and 113 nondemented people. Subjects with systemic inflammatory diseases or who were taking antiinflammatory medications were excluded. All patients underwent extensive medical and detailed neuropsychological examinations at the time their blood was drawn. We found that plasma ACT levels were elevated in AD patients compared with the control group (p = 0.01) and were associated with severity of AD dementia; there was a negative association with the Mattis Dementia Rating Scale (a global measure of cognition) and a positive association with the Clinical Dementia Rating Scale (a global functional assessment). These relationships remained significant after controlling for demographic and genetic variables. When AD subjects were stratified into subgroups by dementia severity, matched by age, education, and gender, increased serum ACT correlated with Clinical Dementia Rating Scale (p = 0.0041) or Mattis Dementia Rating Scale (p = 0.0031) scores. ACT measurements in cerebrospinal fluid from an additional 34 AD cases and 16 controls showed elevated levels (p = 0.02) in AD. There was a negative correlation (p = 0.037) between cerebrospinal fluid ACT levels and clinical severity as measured by the Mini-Mental State Examination. Our results demonstrate that peripheral ACT levels are elevated in AD, but not in dementias other than AD, and they increase with progression of AD dementia. Although not useful as a diagnostic biomarker, ACT may reflect disease severity and may be helpful as a within subject biomarker in interventions (particularly with antiinflammatory agents) directed at slowing or halting progression of disease.

Aged↗
PubMed2003

Determination of patterns of biologically relevant aldehydes in exhaled breath condensate of healthy subjects by liquid chromatography/atmospheric chemical ionization tandem mass spectrometry.

A method for the simultaneous determination of several classes of aldehydes in exhaled breath condensate (EBC) was developed using liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (LC/APCI-MS/MS). EBC is a biological matrix obtained by a relatively new, simple and noninvasive technique and provides an indirect assessment of pulmonary status. The measurement of aldehydes in EBC represents a biomarker of the effect of oxidative stress caused by smoke, disease, or strong oxidants like ozone. Malondialdehyde (MDA), acrolein, alpha,beta-unsaturated hydroxylated aldehydes [namely 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE)], and saturated aldehydes (n-hexanal, n-heptanal and n-nonanal) were measured in EBC after derivatization with 2,4-dinitrophenylhydrazine (DNPH). Atmospheric pressure chemical ionization of the analytes was obtained in positive-ion mode for MDA, and in negative-ion mode for acrolein, 4-HHE, 4-HNE, and saturated aldehydes. DNPH derivatives were separated on a C18 column using variable proportions of 20 mM aqueous acetic acid and methanol. Linearity was established over 4-5 orders of magnitude and limits of detection were in the 0.3-1.0 nM range. Intra-day and inter-day precision were in the 1.3-9.9% range for all the compounds. MDA, acrolein and n-alkanals were detectable in all EBC samples, whereas the highly reactive 4-HHE and 4-HNE were found in only a few samples. Statistically significant higher concentrations of MDA, acrolein and n-hexanal were found in EBC from smokers.

Air Pressure↗
PubMed2005

Soluble p185(HER-2) in patients with malignant bone tumours.

BACKGROUND: This study was initiated to test the hypothesis that soluble p185(HER-2) could be of value as a diagnostic or predictive marker for patients with malignant bone tumours. PROCEDURE: Sera of 35 patients with high-grade malignant osteosarcoma (n = 27) and Ewing Sarcoma (n = 8) were tested at the time of diagnosis by ELISA and compared with sera of controls (n = 38) and clinical data. RESULTS: In patients with osteosarcoma and Ewing Sarcoma, levels of sp185(HER-2) did not differ significantly from levels in controls. These results were irrespective of the type of tumour, survival chemotherapy or other clinical variables. CONCLUSION: p185(HER-2) serum levels do not appear to be of diagnostic or predictive value for differentiation of high-grade osteosarcoma and Ewing Sarcoma.

Adolescent↗
PubMed2005

Carotid atherosclerosis is associated with enhanced beta-chemokine levels in patients on continuous ambulatory peritoneal dialysis.

Increased oxidative stress (SOX) has been reported in continuous ambulatory peritoneal dialysis (CAPD) patients, but its influence on beta-chemokine levels and progression of atherosclerosis remains unknown. We determined three distinct SOX markers: Cu/Zn superoxide dismutase (Cu/Zn SOD), total peroxide and autoantibodies against oxidized LDL (OxLDL-Ab); high sensitivity C-reactive protein (hs CRP); beta-chemokines: monocyte chemoattractant protein-1 (CCL2), macrophage inflammatory proteins (CCL3 and CCL4) and regulated upon activation, normal T cell expressed and secreted (CCL5) and the intima-media thickness (IMT) values in CAPD patients both with and without cardiovascular disease (CVD) and healthy controls. CAPD patients both with and without CVD had significantly increased IMT (p<0.001 and <0.01), Cu/Zn SOD (both p<0.001) and CCL2 levels (p<0.001 and <0.01, respectively) as compared to controls. CCL4 (p<0.01) and hs CRP (p<0.05) were increased only in patients with CVD, whereas there were no differences in the total peroxide, OxLDL-Ab and CCL3 levels between patients and controls. CCL5 concentrations were significantly decreased in both patients subgroup (both p<0.001) versus controls. Multivariate analysis showed that age (p<0.001), male sex (p<0.01), CCL4 and CCL2 levels (both p<0.05) were the independent variables linked to IMT values. Our data suggest a possible role of enhanced beta-chemokine levels in the carotid atherosclerosis in patients treated with CAPD, in addition to age and male sex.

Biomarkers↗
PubMed2006

Relative copy number gain of MYC in diagnostic needle biopsies is an independent prognostic factor for prostate cancer patients.

OBJECTIVES: We have recently shown using comparative genomic hybridization (CGH) that 8q gain is an independent predictor of poor survival for prostate cancer patients. Because CGH may be difficult to implement in the clinical practice, we tested the feasibility of using a three-color fluorescent assay to assess 8q status in diagnostic, paraffin-embedded biopsy samples from prostate cancer patients. METHODS: Fluorescence in situ hybridization with a dual-color probe flanking the MYC gene at 8q24 and a control probe for chromosome 18 was performed in a retrospective series of paraffin-embedded biopsies from 60 prostate cancer patients. The prognostic significance of 8q status was assessed by calculating disease-specific survival curves for these patients. RESULTS: Whereas 44 (73%) samples displayed copy number gains of the MYC gene, a MYC/CEP18 ratio > or = 1.5 was detected in 36 (60%) samples. Kaplan-Meier curves with log-rank test showed that patients whose tumors displayed MYC/CEP18 ratio > or = 1.5 had a significantly worse disease-specific survival (p=0.003). The dual-color labelling of the MYC probe further allowed us to detect structural rearrangements of this gene in six (10%) carcinomas. CONCLUSIONS: We show that a standard fluorescent protocol can successfully be applied to diagnostic needle biopsies to identify relative 8q gain in prostate carcinomas and that patients with a MYC/CEP18 ratio > or = 1.5 present a significantly higher risk of dying from the disease. The prognostic significance of this genetic variable was seen even for patients with Gleason score 7 or clinical stage II/III carcinomas, whose clinical behavior is currently difficult to predict.

Aged↗
PubMed1996

Human recombinant interleukin-4 (HurIL-4) improves SCID mouse reconstitution with human peripheral blood lymphocytes.

The application of human-scid mouse chimera (hu-scid) technology has some limitations, because of the variable amounts and functional heterogeneity of human cells recovered from engrafted mice. Attempts to optimize the construction of hu-scid chimeras with human peripheral blood mononuclear cells (Hu-PBMC) by using in vivo anti-asialo GM1 antibody treatment in mice in order to eliminate natural killer cells have been published by other authors with interesting results. In this study, Hu-PBMC were incubated in vitro with human recombinant interleukin-4 (HurIL-4) or human recombinant interleukin-2 (HurIL-2) for two hours and were intraperitoneally transferred into scid mice. Total human IgM and IgG levels in hu-scid sera, human cell markers in the thymus and in the spleen of grafted mice were considered as parameters of successful engraftment. HurIL-4 significantly enhanced human immunoglobulin production while HurIL-2 did not show any obvious effect. Human cell markers (CD2 and CD19) were significantly higher in the group of HurIL-4 treated Hu-PBMC than in the other groups, despite the high variability in human cell proliferation in the recipients. Thus, HurIL-4 can be used as an adjuvant growth factor which improves successful engraftment of human peripheral blood lymphocytes in scid mice.

Animals↗
PubMed2002

Role of biological markers in the clinical outcome of colon cancer.

We investigated a number of biological markers, evaluated under strict intralaboratory quality control conditions, in terms of their role in predicting clinical outcome of patients with colon cancer treated with 5-FU-containing regimens. Colon cancer tissue from 263 patients enrolled onto two randomised clinical trials were studied for their cytofluorimetrically determined DNA content and their immunohistochemically evaluated microvessel density, vascular endothelial growth factor expression, thymidylate synthase expression and tumour lymphocyte infiltration. Disease-free survival and overall survival of patients were analysed as a function of the different variables. At a median follow up of 57 months, age, gender and Dukes' stage showed an impact on disease-free survival, whereas no biological marker emerged as an indicator of better or worse disease-free survival. Only histological grade and Dukes' stage were found to influence overall survival. The different biological variables, studied with particular attention for determination reliability, proved to have no impact on the clinical outcome of patients with colon cancer. Therefore, other markers must be identified to complement clinico-pathological variables in the management of this disease.

Adenocarcinoma↗
PubMed2000

Clinical markers of serious illness in young infants: a multicentre follow-up study.

OBJECTIVE: To perform a multicentre follow-up study to determine if previously identified markers of serious illness in early infancy were robust and statistically reliable. METHODS: Infants aged 1 week to 26 weeks presenting to the Emergency Departments of the Royal Children's Hospital and two Melbourne metropolitan hospitals were seen over a 12-month period. Eleven clinical markers as well as their temperature were documented by nursing staff and resident medical officers. Serious illness was defined if infants had a positive body fluid bacterial culture, a positive chest X-ray or if significant treatment was required in hospital. The predictive values, sensitivity and specificity for the individual and the best combination of clinical markers were determined. RESULTS: Assessments (3806) were performed with 312 infants being assessed as seriously ill (8.2%). The combination of either drowsiness on history or examination, pallor on history or examination, breathing difficulty (chest wall recession), temperature above 38 degrees C and a lump being present, identified 82.5% of all babies deemed subsequently to be seriously ill. The positive predictive value of an infant who was febrile, drowsy and pale on examination was 70.7% (previous study 74%). CONCLUSIONS: This study confirmed the high individual predictive value of arousal variables, pallor, and chest wall recession, especially when associated with fever, reaffirming their utility in the recognition of serious illness in infants under 6 months of age.

Biomarkers↗