Comparison of three assays for quantifying S-100B in serum

BackgroundSerum S-100B has clinical value in monitoring malignant melanoma and in monitoring and predicting outcomes in patients with traumatic brain injury.MethodsAnalytical performance characteristic and split-sample method comparison studies for three commercial S-100B immunoassays (CanAg® S100, Sangtec® 100, YK150 Human S-100 β) were performed. Reference intervals (97.5th percentile) for each assay were established by non-parametric analysis of results from healthy volunteers.ResultsLinearity results were slope = 1.014, intercept = 65.1, r² = 0.999 for the Sangtec assay; slope = 1.038, intercept = 31.1, r² = 0.999 for the CanAg assay; slope = 1.123, intercept = ? 105.4, r² = 0.997 for the YK150 assay. Within-run CVs were ≤ 5.7, ≤ 6.3 and ≤ 10.8 for the Sangtec, CanAg and YK150 ELISAs, respectively. Between-run CVs were ≤ 11.3, ≤ 5.9 and ≤ 9.5, respectively. Upper reference interval limits of 141, 96 and 735 ng/l S-100B were established for the Sangtec, CanAg and YK150 ELISAs, respectively. Deming regression generated the following: CanAg vs. Sangtec, slope = 0.339, intercept = 24.1, r² = 0.932; YK150 vs. Sangtec, slope = 0.266, intercept = ? 140.0, r² = 0.690; YK150 vs. CanAg, slope = 1.376, intercept = ? 13.1, r² = 0.860.ConclusionsThe configurations, procedures and performance characteristics of the Sangtec and CanAg S-100B ELISAs are comparable and better than those of the YK150 assay. Poor agreement and large biases prevent interchangeable use of results.     

Cytokine elevations in acute coronary syndrome and ovarian cancer: a mechanism for the up-regulation of the acute phase proteins in these different disease etiologies

Objectives:To identify if a common set of cytokines is elevated in both ovarian cancer and acute coronary syndrome (ACS).Design and methods:A cytokine array (Randox Ltd) was measured in healthy women (n = 33), women with ACS (n = 21) and ovarian cancer (n = 45).Results:Women with ACS or ovarian cancer had higher concentrations of IL-6, IL-8, VEGF, MCP-1, and EGF as compared to healthy volunteers.Discussion:Common cytokine elevations are present in both ACS and ovarian cancer.     

Measurement of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 after delayed separation of whole blood samples

Objectives:Epidemiological studies benefit from unbiased blood specimens collected with minimal cost and effort of blood collection and storage. We evaluated the stability of IGF-1 and IGFBP-3 in whole blood samples stored at room temperature to justify delays in blood processing.Design and methods:Total IGF-1 and IGFBP-3 levels were measured in EDTA plasma (n = 12), heparin plasma (n = 12) and serum (n = 10) samples of healthy volunteers after blood processing delays up till 14 days. Stability of measured IGF-1 and IGFBP-3 levels was tested by paired t-test and a linear mixed effect model.Results:Longitudinal analysis showed that IGF-1 levels were not significantly affected by blood processing delays in EDTA tubes (p = 0.18) and IGFBP-3 levels were marginally stable (p = 0.06). In heparin plasma and serum, however, IGF-1 increased over time of delayed processing and IGFBP-3 levels tended to decrease (p < 0.01).Conclusion:Total IGF-1 and IGFBP-3 levels are stable in whole blood collected in EDTA tubes at room temperature up till 7 days, allowing a delay in blood processing to reduce costs in large multi-center studies.     

Serum heat shock protein 70 levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in women with preeclampsia

BackgroundWe have previously reported that serum levels of 70 kDa heat shock protein (Hsp70, HSPA1A) are increased and reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. The purpose of this study was to determine whether increased serum Hsp70 concentrations in women with preeclampsia are related to circulating levels of cytokines, chemokines, adhesion molecules and angiogenic factors, the key players in the pathogenesis of the disease.MethodsSixty preeclamptic patients and 60 normotensive, healthy pregnant women were involved in this case-control study. Levels of Hsp70 (HSPA1A) and transforming growth factor (TGF)-beta1 in maternal sera were assessed by ELISA. Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by multiplex suspension array. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were measured by electrochemiluminescence immunoassay. For statistical analyses, the Mann–Whitney U-test, the Fisher exact and Pearson chi-square tests, the Spearman rank order correlation, multiple linear regression and logistic regression were applied.ResultsSerum levels of Hsp70 were significantly higher in preeclamptic patients than in healthy pregnant women. Additionally, most of the measured inflammatory variables differed significantly between the two study groups except for serum IL-1beta and TGF-beta1 levels and IL-18/IL-12p70 and IL-12p70/IL-12p40 ratios, indicating a bias toward a pro-inflammatory status in preeclampsia. Preeclamptic patients had significantly higher sFlt-1 levels and sFlt-1/PlGF ratio and significantly lower PlGF concentrations as compared to healthy pregnant women. In the preeclamptic group, serum Hsp70 concentrations showed significant correlations with serum levels of IL-12p40 (R = 0.59, p < 0.001), MCP-1 (R = 0.43, p < 0.001), ICAM-1 (R = 0.39, p = 0.0020) and VCAM-1 (R = 0.46, p < 0.001). Furthermore, elevated serum Hsp70 level and sFlt-1/PlGF ratio had a synergistic (joint) effect in the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone.ConclusionsIncreased serum Hsp70 concentrations in women with preeclampsia were associated with pro-inflammatory changes in circulating cytokine profile, suggesting that circulating Hsp70 might contribute to the development of the excessive systemic inflammatory response characteristic of the maternal syndrome of the disease.     

Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome

ObjectivesOur aim was to explore (i) the difference in concentration of IL-6, TNF-α and IL-10 between acute ischemic stroke patients and control individuals; (ii) the association of plasma cytokine concentration with stroke severity at admission assessed by NIHSS and stroke outcome in 90 days assessed by Barthel index (BI) and modified Rankin scale (mRS).Materials and methodsStudy included 68 stroke patients admitted within 12 h of symptoms onset and 71 controls.ResultsIL-6 was increased in patients relative to controls (P = 0.035) and this increase was associated with severe stroke (P = 0.007) and worse outcome (P = 0.030 and 0.019; assessed by BI and mRS, respectively), whereas IL-10 was decreased (P = 0.044) and associated with better outcome (P = 0.043). TNF-α did not differ between studied groups (P = 0.302).ConclusionsIncreased IL-6 and reduced IL-10 concentrations are present in early stroke period and are associated with a degree of neurological deficit and/or stroke outcome.     

Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery

ObjectivesTo investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics.Design and methodsProspective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 ? 174 G/C polymorphism was genotyped.ResultsSerum BDNF concentrations decreased (P = 0.048), correlated with TGF-β1 (r = 0.610 at T1, r = 0.493 at T2, r = 0.554 at T3). Plasma BDNF concentrations raised (P = 0.049), correlated with IL-6 and TNF-α at T1 (r = 0.495 and r = 0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 ? 174 G/C genotype.ConclusionSerum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.     

Serum soluble Fas levels in patients with autoimmune rheumatic diseases

Objective:The role of the serum soluble Fas (sFAS) system is unclear in diagnosis of several autoimmune rheumatic diseases although there are present contradictory reports on the levels of serum sFas. We therefore assessed levels of sFAS in serum of patients with autoimmune rheumatic diseases.Patients and methods:We analyzed sFas levels and their relationship to clinical and laboratory data in patients with systemic lupus erythematosus (SLE, n = 32), rheumatoid arthritis (RA, n = 28), Sjögren's syndrome (SS, n = 20) systemic sclerosis (SSc, n = 21), polymyositis/dermatomyositis (PM/DM, n = 15). Patients with osteoarthritis (OA, n = 20) and healthy volunteers (n = 20) were used as controls. Serum levels of sFAS were determined by ELISA. sFas levels greater than mean (normals) + 2 SD were considered as elevated.Results:The mean sFas values were found higher in RA, PM/DM and OA than in control although no differences were found in SSc and SS patients. The mean sFas levels in SLE patients were lower than healthy controls. Elevated sFas rates in RA, PM/DM and SS were found to be 21.4%, 60%, 10% higher than in healthy controls, respectively. sFas levels in SLE and SSc did not differ from control values. Mean sFas levels did not show significant difference between active and inactive patients in all disease groups except PM/DM, RA and OA. No correlations of sFas with relevant disease subsets, laboratory findings and treatment modalities were found.Conclusions:The findings indicate that the serum sFas molecule may provide a useful additional marker for presence and assessment of disease in patients with RA and PM/DM.     

Synergistic effects of the polymorphisms in the PAI-1 and IL-6 genes with smoking in determining their associated risk with coronary artery disease

ObjectivesTo assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk.Design and methodThe study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method.ResultsThe frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p = 0.04, OR = 1.35). Also the 5G allele carriers (4G5G + 5G5G) were more frequent in patients than in controls (p = 0.03, OR = 1.93). The number of women carrying 5G allele was again significantly higher among patients (OR = 10.95 p = 0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p = 0.035, OR = 1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G + 5G5G)+IL-6(CC) and smoking (SIM = 4.18 and p = 0.0005, OR = 9.20, respectively).ConclusionsThere are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.     

Paraoxonase/arylesterase ratio, PON1 192Q/R polymorphism and PON1 status are associated with increased risk of ischemic stroke

Objectives:In recent years, importance of enzyme activity measurements, in addition to genotyping, in epidemiological studies relating paraoxonase 1 (PON1) and vascular disease was emphasized. This is the first report evaluating paraoxonase and arylesterase activities as risk factors for ischemic stroke. In addition, PON1 192Gln(Q)/Arg(R) and 55Leu(L)/Met(M) polymorphisms were also analyzed.Design and methods:The study population was comprised of 108 ischemic stroke patients and 78 controls. Enzyme activities were determined by spectrophotometric assays and for genotyping, standard PCR protocols followed by restriction enzyme digestions were used.Results:The prevalence of the PON1 192RR genotype was increased among stroke patients (16.7%) as compared to controls (9.0%, P = 0.129). Paraoxonase and arylesterase activities and PON1 activity ratio (paraoxonase/arylesterase) were found to be lower in patients than in controls. Logistic regression analysis revealed PON1 activity ratio (odds ratio, OR = 0.697, 95% CI, 0.541 to 0.898, P = 0.005), PON1 192RR genotype (OR = 3.434, 95% CI, 1.159 to 10.178, P = 0.026) and PON1 status (PON1 activity ratio combined with PON1 192RR genotype; OR = 1.406, 95% CI, 1.038 to 1.905, P = 0.028) as significant predictors of stroke.Conclusions:This study identified PON1 activity ratio, PON1 192RR genotype and PON1 status as important risk factors for ischemic stroke.     

Performance evaluation of Siemens ADVIA Centaur enhanced estradiol assay and a split sample comparison with liquid chromatography-tandem mass spectrometry

ObjectivesThe objective of this study was to evaluate the newly developed Siemens ADVIA Centaur® enhanced Estradiol (eE2) assay and compare it with a well-established estradiol liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.Design and methodsThe Siemens eE2 assay was evaluated using the Clinical and Laboratory Standards Institute evaluation protocols. Split patient samples were compared with the eE2 assay, the current ADVIA Centaur E2-6 Ill assay; and LC-MS/MS method by API5000 mass spectrometer.ResultsWithin-run and total imprecision of the eE2 assay demonstrated coefficient of variations of 5.7%, 3.2%, 1.5%, and 10.4%, 7.3%, and 6.8%, at levels of 380, 752, and 2051 pmol/L, respectively. The method comparisons showed: eE2 = 0.903(E2-6 III) –16.2, R² = 0.938, average bias = ? 12.3%; and eE2 = 0.946(LC-MS/MS) + 19.5, R² = 0.925, average bias: 0%.ConclusionThe Siemens eE2 assay correlates well with LC-MS/MS. This method is reliable, and appropriate for routine clinical laboratory use.     

Relationship between circulating cytokine levels and physical or psychological functioning in patients with advanced cancer

ObjectiveTo investigate the relation between functional impairments of cancer patients and circulating cytokines using a multiplex technique.Design and methods50 patients with cancer were assessed using the quality of life (QOL) questionnaire. 27 plasma cytokine levels were determined by using the Bio-Plex array system. The relation to QOL scores was assessed using Chi-square test for categorical variables and univariate linear regression analysis for cytokine levels.ResultsMultivariate analysis showed that interleukin-6 (IL-6) level is a significant independent determinant of physical (β = ? 0.238, P = 0.0126) and cognitive functioning (β = ? 0.462, P = 0.0006) and that vascular endothelial growth factor (VEGF) level is a significant independent determinant of emotional functioning (β = ? 0.414, P = 0.039).ConclusionThis study, in which 27 cytokines are simultaneously tested with cutting edge technology, demonstrates that plasma IL-6 and VEGF are significant independent determinants of functional impairments in patients with cancer.     

Evaluation of circulating vascular endothelial growth factor and soluble adhesion molecules as reliable predictors of native arteriovenous fistula thrombosis in chronic hemodialysis patients

ObjectivesWe evaluated the possibility of using circulating vascular endothelial growth factor (VEGF) and soluble adhesion molecules as reliable predictors of native arteriovenous (AV) fistula thrombosis in chronic hemodialysis (HD) patients.Design and methodsThis study included 62 HD patients (34 with thrombosed and 28 with non-thrombosed AV fistulas) and 21 healthy volunteers. Serum VEGF, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin) were measured using ELISA technique.ResultsVEGF, sVCAM-1, sICAM-1 and sE-selectin median levels were higher in HD patients compared to controls (p = 0.000 for all parameters). Increased median levels of VEGF and sVCAM-1 were demonstrated in HD patients with thrombosed AV fistulas compared to HD patients with non-thrombosed AV fistulas (p = 0.003 and 0.000, respectively). A significant positive correlation has been found between VEGF and sVCAM-1 in HD patients with thombosed AV fistulas (r = 0.525, p = 0.001).ConclusionsThe assessment of serum VEGF and sVCAM-1 might be useful for the identification of the chronic HD patients at an increased risk for native AV fistulas thrombosis. The clinical relevance of these observations warrants further investigations.     

Increased urinary level of oxidized nucleosides in patients with mild-to-moderate Alzheimer's disease

Objective:Oxidative stress may play an important role in the pathogenesis of Alzheimer's disease (AD).Design and methods:To investigate the possible role of oxidative DNA damage in the pathogenesis of AD, we measured the metabolite concentrations of oxidized nucleosides (pseudouridine, 1-methyladenosine, 5-methylcytidine, 5-methyl-2′-deoxycytidine, 3-methyluridine, N², N²-dimethylguanosine, 8-hydroxy-2′-deoxyguanosine, 5-deoxyadenosine and 2-deoxyguanosine) in urine between AD (n = 36) and control subjects (n = 34) using liquid chromatography-mass spectrometry (LC-MS) without urine preparation.Results:In AD, the 3-methyluridine, 1-methyladenosine, 8-hydroxy-2′-deoxyguanosine (p < 0.05, respectively), 2-deoxyguanosine (p < 0.01) and pseudouridine, N², N²-dimethylguanosine (p < 0.001, respectively) were significantly increased when compared with the control subjects.Conclusion:The results indicate that oxidized urinary nucleosides may be useful as biomarkers for AD in early stages.     

Normal range of serum Amphiregulin in healthy adult human females

ObjectivesPrior to large studies in breast cancer patients, we have sought to establish the normal range of a potential serum biomarker, Amphiregulin, in healthy women and to determine whether sampling during the menstrual cycle influences the detected Amphiregulin levels.Design and methodsSerum Amphiregulin levels were quantified using a commercially available ELISA in 85 normal female donors.ResultsThe range of circulating Amphiregulin was 0–4467 pg/mL. The majority of women had no detectable circulating Amphiregulin (n = 54), and only five women had levels exceeding 500 pg/mL. Serum Amphiregulin levels did not vary significantly during the menstrual cycle (n = 7 women).ConclusionsDetection of circulating Amphiregulin in a significant minority of healthy women suggests that it may not have the specificity necessary for a population screening tool; however its potential utility for monitoring response to treatment or disease progression should be examined in breast cancer cases.     

Validation of a simple method of estimating plasma free cortisol: role of cortisol binding to albumin

Objectives:To develop, optimize, and validate a generalized mass action, equilibrium solution that incorporates measured concentrations of albumin as well as cortisol binding globulin (CBG) to estimate free cortisol.Design and methods:Free cortisol was estimated by Coolens method or by cubic equilibrium equation and compared to measured free cortisol, determined by ultrafiltration method, in subjects with septic shock (n = 45), sepsis (n = 19), and healthy controls (n = 10) at 0, 30, and 60 min following administration of cosyntropin (250 mcg). The data set also included repeat testing in 30 subjects following recovery from sepsis/septic shock. The equilibrium dissociation constant for cortisol binding to albumin (K_A) was optimized by non-linear regression. The cubic equilibrium solution was also used to model the influence of cortisol, CBG, and albumin concentration on free cortisol.Results:Compared to measured free cortisol, the cubic solution, using an optimized K_A of 137,800 nM, was less biased than Coolens solution, with mean percent error of ? 23.0% vs. ? 41.1% (paired t test, P < 0.001). Standard deviation values were also significantly lower (Wilks' test, P < 0.001) for the cubic solution (SD 35.8% vs. 40.8% for cubic vs. Coolens, respectively). Modeling studies using the cubic solution suggest an interaction effect by which low concentrations of CBG and albumin contribute to a greater increase in free cortisol than the sum of their independent effects.Conclusions:Mass action solutions that incorporate the measured concentration of albumin as well as CBG provide a reasonably accurate estimate of free cortisol that generalizes to conditions of health as well as a setting of hypercortisolism and low CBG and albumin concentrations associated with septic shock. Modeling studies emphasize the significant contribution of albumin deficiency and albumin-bound cortisol under conditions of CBG-deficiency, and identify a synergistic effect by which combined CBG and albumin deficiency contribute to elevation of free cortisol in septic shock.     

Mitochondrial depolarisation and oxidative stress in rheumatoid arthritis patients

ObjectivesTo investigate mitochondrial membrane integrity, lipid peroxidation and cytotoxicity in peripheral lymphocytes (PL) from rheumatoid arthritis (RA) patients.Design and methodsSouth African black RA patients (HIV^?) were recruited into the study. Mitochondrial membrane potential (Δψ_m) was analysed in PL using the JC-1 dye distribution assay and flow cytometry. Correlations between Δψ_m and clinical parameters were tested for statistical significance. Cytotoxicity (LDH) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) was also determined.ResultsOur findings show significantly elevated levels of cytotoxicity (p = 0.0029) and lipid peroxidation (p = 0.0030) in RA. A significantly higher percentage of circulating PL contained depolarised mitochondria (p = 0.0003) which correlated with disease activity and C-reactive protein levels in patients. Collapse of Δψ_m also negatively correlated to absolute lymphocyte counts (r = ? 0.4041; p = 0.0197).ConclusionThese findings suggest a possible role for mitochondrial membrane alterations in the pathology of RA.     

Comparative study between anion-exchange HPLC and homogeneous assay methods in regard to the accuracy of high- and low-density lipoprotein cholesterol measurement

Objectives:A convenient method based on anion-exchange HPLC was recently developed to determine cholesterol levels of lipoproteins (HDL, LDL, IDL, VLDL, and chylomicron). The present study was performed to compare this HPLC method to homogenous assay in regard to measurement accuracy of HDL and LDL cholesterol.Design and methods:Serum samples (n = 105), including three samples from cholestasis patients, were measured by homogenous assay with Cholestest-LDL and CholestestN-HDL (Daiichi Chemicals, Tokyo) and by HPLC as reported previously (J Lipid Res 2003; 44: 1404–12).Results:The homogenous assay for HDL cholesterol correlated strongly with the HPLC method for HDL cholesterol (r = 0.976). Two samples from cholestasis patients could not be measured by homogenous assay but were measured by HPLC. The homogenous assay for LDL cholesterol correlated modestly with the HPLC method for LDL cholesterol (r = 0.823). Three outlier samples, from cholestasis patients with serum cholesterol levels > 17 mmol/L, were observed in this correlation analysis. Homogenous assay data showed that these LDL cholesterol levels were 15.2–34.7 mmol/L. However, HPLC data showed that these LDL cholesterol levels were 3.6–8.2 mmol/L, and that the major lipoprotein fractions were VLDL and IDL. The difference in LDL cholesterol levels (homogenous assay data minus HPLC data) was positively correlated with VLDL cholesterol levels.Conclusions:When measuring samples from cholestasis patients, homogenous assay may give inaccurate results. In contrast, the HPLC method is likely to be capable of accurately measuring HDL and LDL cholesterol levels without the involving VLDL.     

Lovastatin enhances paraoxonase enzyme activity and quells low-density lipoprotein susceptibility to oxidation in type 2 diabetic nephropathy

Objectives:To investigate the effect of lovastatin therapy and withdrawal on paraoxonase 1 (PON1) and arylesterase (ARE) activities, and low-density lipoprotein cholesterol (LDL-C) susceptibility to oxidation in people with type 2 diabetic nephropathy (T2DN).Design and methods:Lovastatin (20 mg/day) was administered to 30 people with T2DN for 90 days and then withdrawn for 30 days. PON1 and ARE activities were measured by the spectrophotometric method. Susceptibility of LDL-C to oxidation was determined as the production of conjugated dienes.Results:After 90 days of lovastatin intervention, PON1 and ARE activities and LDL-C lag phase were significantly increased (p = 0.004, 0.002, and < 0.001), while after 30 days of lovastatin withdrawal, PON1 and ARE activities and LDL-C lag phase had not changed significantly.Conclusion:Lovastatin therapy improves PON1 and ARE activities, and LDL-C susceptibility to oxidation. Despite withdrawal of lovastatin, PON1 and ARE activities, and LDL-C susceptibility to oxidation remain unchanged in people with T2DN.     

Procalcitonin and C-reactive protein levels as diagnostic tools in febrile patients admitted to a General Internal Medicine ward

Objective: We study the extent to which procalcitonin (Pro-CT) and/or C-reactive protein (CRP) may be helpful in the early triage of febrile patients admitted to a general internal medicine ward.Methods: This is a prospective, observational study on 62 admitted patients in whom a temperature > 38 °C had been observed the day before inclusion.Results: Neither Pro-CT nor CRP was able to discriminate infectious (or bacterial) diseases from the other etiologies as a group, with an area under the ROC curve of 0.63 (95% CI 0.47–0.79, p = 0.15) for Pro-CT and 0.61, (95CI 0.44–0.78, p = 0.23) for CRP.Sensitivity and specificity for Pro-CT varied between 0.59 and 0.67 for a cut-off point of 0.2 ng/mL and 0.03 and 1 for a cut-off point of 10.0 ng/mL.However, in subgroup analysis, Pro-CT was able to discriminate between infectious and inflammatory diseases (Welch two sample t-test t = 2.39, df = 44.3, p = 0.021).     

Association between the -2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and hypertension in Tunisian patients

ObjectivesMonocyte chemoattractant protein-1 (MCP-1:CCL2) has been demonstrated to be involved in the pathophysiology of atherosclerosis and hypertension. This study was aimed to investigate whether the single nucleotide polymorphism (SNP) at ?2518 of the MCP-1 gene promoter region is associated to hypertension in a sample of Tunisian population.Design and methodsA total of 290 Tunisian patients with hypertension and 390 normotensive controls were included in the study. The SNP of the MCP-1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.ResultsA significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 7.2% for the GG genotype, 35.2% for the AG genotype and 57.6% for the AA genotype. Normotensive subjects had a frequency of 3.6% for the GG genotype, 29.7% for the AG genotype and 66.7% for the AA genotype (χ² = 8.02, p = 0.01). The hypertension patient group showed a significant higher frequency of the G allele compared to the controls [0.24 vs. 0.18; OR (95%CI), 1.46 (1.11–1.91), p = 0.004]. The association between the ?2518 G/A polymorphism of MCP-1 gene and hypertension remained significant after adjustment for other well-established cardiovascular risk factors.ConclusionThe present study showed a significant and independent association between the ?2518G/A polymorphism of the MCP-1 gene (presence of G allele) and hypertension in the Tunisian population.