CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia.

RATIONALE: We hypothesized that cluster of differentiation 74 (CD74) downregulation on placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. OBJECTIVE: Preeclamptic pregnancies feature hypertension, proteinuria, and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies. METHODS AND RESULTS: We performed whole-genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By reverse transcriptase-polymerase chain reaction, we confirmed this finding in early-onset (<34 gestational week, n=26) and late-onset (≥34 gestational week, n=24) samples from preeclamptic women, compared with healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry, and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared with controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM, ICAM4, and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naive and activated macrophages lacking CD74 showed a shift toward a proinflammatory signature with an increased secretion of tumor necrosis factor-α, chemokine (C-C motif) ligand 5, and monocyte chemotactic protein-1, when cocultured with trophoblasts compared with control macrophages. Trophoblasts stimulated by these factors express more CYP2J2, sFlt1, TNFα, and IL-8. CD74-knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas, and impaired spiral artery remodeling with fetal growth restriction. CONCLUSIONS: CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation toward a proinflammatory signature and a disturbed crosstalk with trophoblasts.

Sensitive troponin I assay in early diagnosis of acute myocardial infarction.

BACKGROUND: Cardiac troponin testing is central to the diagnosis of acute myocardial infarction. We evaluated a sensitive troponin I assay for the early diagnosis and risk stratification of myocardial infarction. METHODS: In a multicenter study, we determined levels of troponin I as assessed by a sensitive assay, troponin T, and traditional myocardial necrosis markers in 1818 consecutive patients with suspected acute myocardial infarction, on admission and 3 hours and 6 hours after admission. RESULTS: For samples obtained on admission, the diagnostic accuracy was highest with the sensitive troponin I assay (area under the receiver-operating-characteristic curve [AUC], 0.96), as compared with the troponin T assay (AUC, 0.85) and traditional myocardial necrosis markers. With the use of the sensitive troponin I assay (cutoff value, 0.04 ng per milliliter) on admission, the clinical sensitivity was 90.7%, and the specificity was 90.2%. The diagnostic accuracy was virtually identical in baseline and serial samples, regardless of the time of chest-pain onset. In patients presenting within 3 hours after chest-pain onset, a single sensitive troponin I assay had a negative predictive value of 84.1% and a positive predictive value of 86.7%; these findings predicted a 30% rise in the troponin I level within 6 hours. A troponin I level of more than 0.04 ng per milliliter was independently associated with an increased risk of an adverse outcome at 30 days (hazard ratio, 1.96; 95% confidence interval, 1.27 to 3.05; P=0.003). CONCLUSIONS: The use of a sensitive assay for troponin I improves early diagnosis of acute myocardial infarction and risk stratification, regardless of the time of chest-pain onset.

Midregional proadrenomedullin for prediction of cardiovascular events in coronary artery disease: results from the AtheroGene study.

BACKGROUND: Midregional proadrenomedullin (MR-proADM) is a newly identified prognostic marker in heart failure. We evaluated the prognostic impact of MR-proADM in a cohort of patients with symptomatic coronary artery disease according to their clinical presentation. METHODS: We measured baseline MR-proADM concentrations in 2240 individuals from the prospective AtheroGene study and evaluated the prognostic impact on future fatal and nonfatal cardiovascular events during a follow-up period of 3.6 (1.6) years. RESULTS: The sample comprised 1355 individuals with stable angina pectoris (SAP) and 885 with acute coronary syndrome (ACS). A cardiovascular event occurred in 192 people. Individuals presenting with SAP had only slightly lower plasma MR-proADM concentrations than those with ACS (0.53 vs 0.55 nmol/L, P=0.006). MR-proADM showed a moderate association with age, serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), glomerular filtration rate, serum C-reactive protein, hypertension, diabetes, and prevalent multivessel disease (all P<0.0005). Individuals suffering from a cardiovascular event had higher MR-proADM concentrations at baseline in both groups (SAP 0.63 vs 0.53 nmol/L and ACS 0.65 nmol/L vs 0.55 nmol/L, both P<0.0005). Cox regression analysis incorporating various variables of cardiovascular risk and NT-proBNP revealed a hazard ratio of 1.4 (95% CI 1.2-1.6; P<0.0005) per increment of MR-proADM by 1SD. In risk models for secondary prevention, MR-proADM provided information comparable to that of NT-proBNP. CONCLUSIONS: MR-proADM is an independent predictor for future cardiovascular events in patients with symptomatic coronary artery disease, providing information comparable to NT-proBNP for secondary risk stratification.

Differences in serum zn levels in acutely ill and recovered adolescents and young adults with anorexia nervosa--a pilot study.

Preliminary evidence suggests that changes in zinc (Zn) metabolism are associated with anorexia nervosa (AN). However, data are scarce regarding potential differences in serum Zn concentrations in adolescent and young adult patients with AN. It was the aim of the present pilot study to compare serum Zn concentrations between acutely ill and remitted adolescent and young adult female patients with AN and female controls. Zn concentrations were higher in remitted compared with acutely ill patients. Zn concentrations were also higher in remitted patients compared with controls, but there was no significant difference in Zn concentrations between acutely ill patients and controls. The present study provides preliminary evidence for differences in serum Zn status in recovered patients with AN. These differences are likely influenced by reported food preferences, in particular as regards Ca²âº and phosphorus-containing foods. However, because of limited statistical power, future research involving larger samples is necessary.

Multiple marker approach to risk stratification in patients with stable coronary artery disease.

AIMS: multimarker approaches for risk prediction in coronary artery disease have remained inconsistent. We assessed multiple biomarkers representing distinct pathophysiological pathways in relation to cardiovascular events in stable angina. METHODS AND RESULTS: we investigated 12 biomarkers reflecting inflammation [C-reactive protein, growth-differentiation factor (GDF)-15, neopterin], lipid metabolism (apolipoproteins AI, B100), renal function (cystatin C, serum creatinine), and cardiovascular function and remodelling [copeptin, C-terminal-pro-endothelin-1, mid-regional-pro-adrenomedullin (MR-proADM), mid-regional-pro-atrial natriuretic peptide (MR-proANP), N-terminal-pro-B-type natriuretic peptide (Nt-proBNP)] in 1781 stable angina patients in relation to non-fatal myocardial infarction and cardiovascular death (n = 137) over 3.6 years. Using Cox proportional hazards models and C-indices, the strongest association with outcome for log-transformed biomarkers in multivariable-adjusted analyses was observed for Nt-proBNP [hazard ratio (HR) for one standard deviation increase 1.65, 95% confidence interval (CI) 1.28-2.13, C-index 0.686], GDF-15 (HR 1.59, 95% CI 1.25-2.02, C-index 0.681), MR-proANP (HR 1.46, 95% CI 1.14-1.87, C-index 0.673), cystatin C (HR 1.39, 95% CI 1.10-1.75, C-index 0.671), and MR-proADM (HR 1.63, 95% CI 1.21-2.20, C-index 0.668). Each of these top single markers and their combination (C-index 0.690) added predictive information beyond the baseline model consisting of the classical risk factors assessed by C-index and led to substantial reclassification (P-integrated discrimination improvement <0.05). CONCLUSION: comparative analysis of 12 biomarkers revealed Nt-proBNP, GDF-15, MR-proANP, cystatin C, and MR-proADM as the strongest predictors of cardiovascular outcome in stable angina. All five biomarkers taken separately offered incremental predictive ability over established risk factors. Combination of the single markers slightly improved model fit but did not enhance risk prediction from a clinical perspective.

Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction.

CONTEXT: Introduction of highly sensitive troponin assays into clinical practice has substantially improved the evaluation of patients with chest pain. OBJECTIVE: To evaluate the diagnostic performance of a highly sensitive troponin I (hsTnI) assay compared with a contemporary troponin I (cTnI) assay and their serial changes in the diagnosis of acute myocardial infarction (AMI). DESIGN, SETTING, AND PATIENTS: A total of 1818 patients with suspected acute coronary syndrome were consecutively enrolled at the chest pain units of the University Heart Center Hamburg, the University Medical Center Mainz, and the Federal Armed Forces Hospital Koblenz, all in Germany, from 2007 to 2008. Twelve biomarkers including hsTnI (level of detection, 3.4 pg/mL) and cTnI (level of detection, 10 pg/mL) were measured on admission and after 3 and 6 hours. MAIN OUTCOME MEASURES: Diagnostic performance for AMI of baseline and serial changes in hsTnI and cTnI results at 3 hours after admission to the emergency department. RESULTS: Of the 1818 patients, 413 (22.7%) were diagnosed as having AMI. For discrimination of AMI, the area under the receiver operating characteristic (ROC) curve was 0.96 (95% CI, 0.95-0.97) for hsTnI on admission and 0.92 (95% CI, 0.90-0.94) for cTnI on admission. Both were superior to the other evaluated diagnostic biomarkers. The use of hsTnI at admission (with the diagnostic cutoff value at the 99th percentile of 30 pg/mL) had a sensitivity of 82.3% and a negative predictive value (for ruling out AMI) of 94.7%. The use of cTnI (with the diagnostic cutoff value at the 99th percentile of 32 pg/mL) at admission had a sensitivity of 79.4% and a negative predictive value of 94.0%. Using levels obtained at 3 hours after admission, the sensitivity was 98.2% and the negative predictive value was 99.4% for both hsTnI and cTnI assays. Combining the 99th percentile cutoff at admission with the serial change in troponin concentration within 3 hours, the positive predictive value (for ruling in AMI) for hsTnI increased from 75.1% at admission to 95.8% after 3 hours, and for cTnI increased from 80.9% at admission to 96.1% after 3 hours. CONCLUSIONS: Among patients with suspected acute coronary syndrome, hsTnI or cTnI determination 3 hours after admission may facilitate early rule-out of AMI. A serial change in hsTnI or cTnI levels from admission (using the 99th percentile diagnostic cutoff value) to 3 hours after admission may facilitate an early diagnosis of AMI.

Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the AtheroGene study.

AIMS: Chronic kidney disease is associated with increased risk of cardiovascular disease. Cystatin C is a promising marker to reliably mirror renal function. The role of cystatin C in patients with coronary artery disease (CAD) and normal or mildly reduced kidney function is the subject of current investigation. METHODS AND RESULTS: In 2162 patients, over the whole spectrum of CAD, baseline cystatin C concentrations were measured. Patients with an estimated glomerular filtration rate of < or =60 mL/min per 1.73 m(2) (n = 295) were excluded. In patients with complete follow-up information (n = 1827), 66 cardiovascular deaths were registered during a median follow-up of 3.65 years. Logarithmically transformed, standardized cystatin C was associated with cardiovascular death [hazard ratio: 1.94, 95% confidence interval (CI): 1.59-2.37, P < 0.001]. A potential threshold effect was observed; patients in the upper quartile had a 3.87-fold (95% CI: 2.33-6.42; P < 0.001) risk of mortality compared with the pooled lower quartiles. This risk association remained robust after adjustment for potential confounders including classical risk factors and N-terminal pro B-type natriuretic peptide. Serum creatinine was not associated with the outcome in this group of patients with normal renal function. CONCLUSION: Results of this prospective study show that cystatin C is a potent predictor of cardiovascular mortality beyond classical risk factors in patients with CAD and normal or mildly reduced kidney function.

Case Report of Presumed (In)voluntary Capsaicin Intoxication Mimicking an Acute Abdomen.

BACKGROUND: The clinical features of a presumed capsaicin intoxication have not been reported so far. Case Presentation. A 27-year-old man took part in a qualifying for a competition in spicy food tolerance. During this qualifying, he swallowed 4 chili peppers type Bhut jolokia (about 1 million Scoville units) and other extremely spicy foods; the total amount of capsaicin ingested (roughly calculated retrospectively) accounted for at least 600 mg. After 2½ hours, the patient developed severe abdominal pain, which led to hospital admission. In contrast to the severe symptoms, clinical, laboratory, and imaging examinations (ultrasound and plain X-ray of the abdomen) did not reveal any significant abnormalities. Treatment with analgesics resulted in complete regression of the abdominal pain within 30 hours. CONCLUSIONS: The clinical picture in the view of pharmacological investigations on intestinal capsaicin infusions suggests that excessive doses of capsaicin can induce severe abdominal pain; the prolonged symptoms were probably due to the failure to vomit. Thus, a capsaicin intoxication must be considered in the differential diagnosis of an acute abdomen.

Selenium supplementation improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease The SElenium Therapy in Coronary Artery disease Patients (SETCAP) Study.

BACKGROUND: Selenium is a central determinant of antioxidative glutathione peroxidase 1 (GPx-1) expression and activity. The relevance of selenium supplementation on GPx-1 in coronary artery disease (CAD) needs to be established. We assessed the effect of selenium supplementation on GPx-1 in cell culture and on endothelial function in a prospective clinical trial. METHODS: Human coronary artery endothelial cells were incubated with 5.78 to 578 nmol/L sodium selenite, Se-methyl-selenocysteine hydrochloride, or seleno-l-methionine. Glutathione peroxidase 1 mRNA and protein expression and activity were measured. Coronary artery disease patients (n = 465) with impaired endothelial function (flow-mediated dilation [FMD] <8%) were randomly assigned to receive 200 or 500 microg sodium selenite daily or matching placebo during a 12-week period. We tested the effect on red blood cell GPx-1 activity and brachial artery FMD. Furthermore, differences in biomarkers of oxidative stress and inflammation were measured. RESULTS: Sodium selenite and Se-methyl-selenocysteine hydrochloride increased GPx-1 protein and activity in a dose-dependent manner (P < .0001). The intention-to-treat groups comprised 433 CAD patients. Glutathione peroxidase 1 activity increased from 37.0 U/gHb (31.3-41.7) to 41.1 U/gHb (35.2-48.4) (P < .0001) in the 200 microg and from 38.1 U/gHb (33.2-43.8) to 42.6 U/gHb (35.0-49.1) (P < .0001) in the 500 microg sodium selenite group treated for 12-weeks. No relevant changes were observed for FMD or biomarkers of oxidative stress and inflammation. CONCLUSIONS: Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved.

A multicenter evaluation of a new quantitative highly sensitive D-dimer assay for exclusion of venous thromboembolism.

D-dimer testing is widely applied for exclusion of deep-vein thrombosis (DVT) and pulmonary embolism (PE). We report on a multicenter performance evaluation of a new particle-enhanced immunoassay, Innovance D-Dimer. Innovance D-Dimer assay was performed in 1,543 frozen samples from outpatients suspected of DVT and/or PE enrolled in three management studies as well as in a routine clinical practice. Samples were assayed on BCS/BCS XP, BCT as well as Sysmex CA-7000, CA-1500 and CA-560 analyzers (cut-off on all analyzers: 0.5 mg/l). Stratus CS D-Dimer and Vidas D-Dimer Exclusion were used for comparison. The precision study indicated total coefficients of variation ranging from 2.1% to 8.4% depending on the analyzer and on the sample. Sensitivity and negative predictive values were above 99% and their lower 95% confidence interval were equal or above 97.4% and 98.6%, respectively. Specificity ranged from 38.2% to 40.4% and the respective lower 95% confidence intervals from 35.5% to 37.7%. Area under the curve was 0.90 for all assay systems except for Innovance D-Dimer with BCT (0.89). Two samples from patients with distal DVT tested negative with all assay systems. One patient with high pre-test clinical probability and proximal DVT tested negative with Vidas D-Dimer Exclusion. Our data indicate that the performances of Innovance D-Dimer, regardless of the analyzer, are similar to the reference methods, and that this assay can be used for the exclusion of venous thromboembolic disease.

Comparison of bivalirudin, enoxaparin, and unfractionated heparin in preventing cardiac catheter thrombosis. Results of an in-vitro study.

Bivalirudin, a direct thrombin inhibitor binds specifically and reversibly to both fibrin-bound and unbound thrombin. Bivalirudin is approved for use as an anticoagulant in patients undergoing percutaneous coronary intervention. The OASIS-5 trial presented a significant increase in cardiac catheter thrombosis for the pentasaccharid fondaparinux compared to enoxaparin. Catheter thrombosis has never been reported in any trial using bivalirudin. Our study compared the development of catheter thrombosis for bivalirudin, enoxaparin, and unfractionated heparin in a controlled in-vitro environment. Ten healthy male volunteers were pretreated with aspirin 500 mg 2 hours before venesection of 50 ml of blood. The seven groups of anticoagulant combinations tested were: UFH, UFH + eptifibatide, enoxaparin, enoxaparin + eptifibatide, bivalirudin bolus, bivalirudin + eptifibatide, bivalirudin bolus + continuous infusion. The blood/anticoagulant mix continuously circulated through a cardiac guiding catheter for 60 minutes or until the catheter became blocked with thrombus. Thrombus development was assessed by weighing each catheter before and after the procedure. Electron microscopy was used to quantify the degree of erythrocyte, platelet and fibrin deposition. Following anticoagulation with bolus dose bivalirudin, the catheter was invariably occluded with thrombus after 33 minutes of circulation. However, a continuous infusion of Bivalirudin prevented the development of occlusive catheter thrombosis. In the bolus bivalirudin group the mean thrombus weight was significantly greater than in all other groups (p-value < 0.01 in all analyses). Bivalirudin given as a bolus was not sufficient to prevent cardiac catheter thrombosis in our in-vitro study. However, a continuous infusion of bivalirudin had similar anti-thrombotic efficacy compared to other treatment strategies.

Prothrombinase-induced clotting time assay for determination of the anticoagulant effects of unfractionated and low-molecular-weight heparins, fondaparinux, and thrombin inhibitors.

The prothrombinase-induced clotting time assay (PiCT, Pentapharm, Basel, Switzerland) is a clotting assay sensitive to factor Xa and factor IIa inhibitors. It is based on the addition of factor Xa and snake venom RVV-V (Russell viper venom factor V activator) specifically activating factor V and phospholipids to platelet-poor plasma. Following an incubation time, the mixture is recalcified and the clotting time is determined. An almost linear dose-response and high sensitivity of the assay for unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), r-hirudin, and argatroban was found. Fondaparinux showed a nonlinear dose-response. By using ex vivo samples, the following Pearson correlation coefficients were found: r=0.85 between amidolytic anti-Xa and PiCT for 120 LMWH and 24 control samples; r=0.86 between amidolytic anti-Xa activity and PiCT for 68 UFH and 24 control samples; and r=0.94 between ECT and PiCT for 38 hirudin samples. Thus, PiCT is a promising assay for the monitoring of anticoagulants inhibiting factor Xa and/or factor IIa.

In-vitro comparison of fondaparinux, unfractionated heparin, and enoxaparin in preventing cardiac catheter-associated thrombus.

BACKGROUND: The Organization to Assess Strategies in Acute Ischemic Syndromes trials showed that fondaparinux (fonda) is at least as effective and safe as unfractionated heparin (UFH) and enoxaparin (enoxa) in acute coronary syndromes. Unexpectedly, there was an increase in catheter-related thrombus formation during percutaneous coronary interventions in fonda-treated patients. METHODS: Ten healthy male volunteers were pretreated with aspirin 500 mg 2 h before venesection of 50 ml of blood. Eight groups of anticoagulant (combinations) were tested and volunteers donated blood eight times, thus, acting as their own controls. The groups were UFH, UFH+eptifibatide, enoxa, enoxa+eptifibatide, fonda, fonda+eptifibatide, fonda+(half-therapeutic) UFH, and fonda+eptifibatide+(half-therapeutic) UFH. The blood/anticoagulant mix was kept at 37 degrees C and continuously circulated through a guiding catheter for 60 min or until the catheter became blocked with thrombus. Thrombus development was assessed by weighing each catheter before and after the procedure. Electron microscopy of the catheter lining was used to quantify the degree of erythrocyte and fibrin deposition. RESULTS: Despite fonda anticoagulation, catheters were invariably occluded by thrombus before the 60 min perfusion period had elapsed. Thrombotic catheter occlusion occurred even with higher fonda concentrations and combined fonda/eptifibatide use. All other combinations (including fonda and half-therapeutic UFH) ensured catheter patency for 60 min. Furthermore, thrombus weight and the cell/fibrinogen counts were significantly increased in fonda and fonda+eptifibatide compared with other treatment groups. CONCLUSION: Treatment with fonda, even in combination with eptifibatide, was not sufficient to prevent cardiac catheter thrombus development in our in-vitro study. However, the combination of fonda with 'half' therapeutic dosages of UFH were as efficient as other treatment strategies in preventing thrombus formation.

Bilirubin, urobilinogen, pancreas elastase and bile acid in drain fluid. The GBUP-study: Analysis of biomarkers for a colorectal anastomotic leakage.

PURPOSE: A colorectal anastomotic leakage (CAL) is a major complication after colorectal surgery and leads to high rates of morbidity and prolonged hospital stay. The study aims to evaluate the benefit of using bilirubin, urobilinogen, pancreas elastase and bile acid in the drain fluid (DF) as a predictive marker for the CAL. METHODS: From June 2015 to October 2017 100 patients, who underwent left hemicolectomy (LH), sigma resection (SR), high anterior resection (HAR), low anterior resection (LAR) or reversal of Hartmann's Procedure (ROHP) were included in this monocentric non-randomized prospective clinical trial. During the first four postoperative days (POD) the concentration of bilirubin, urobilinogen, pancreas elastase and bile acid in the DF was measured. RESULTS: In total 100 patients were recruited. 17 were excluded due to intraoperative decisions to conduct a protective stoma. 6 patients had a CAL. The patients of the control group (n = 77) and the patients who suffered from a CAL (n = 6) had no increased concentration of urobilinogen and pancreas elastase in the DF. The concentration of bile acid in the DF of the patients who suffered from a CAL differed from those of the control group on the 4th POD (p = 0.055).The concentration of bilirubin in the DF of the patients who suffered from a CAL significantly differed from those of the control group on the 1st POD (p = 0.031) and on the 3rd POD (p = 0.041). CONCLUSION: Bilirubin and bile acid in the DF may function as a predictive marker for a CAL.

Resistin, acute coronary syndrome and prognosis results from the AtheroGene study.

OBJECTIVE: Resistin, an adipocyte and macrophage derived cytokine, causes insulin resistance and glucose intolerance. We investigated the impact of resistin as a diagnostic marker in patients with acute coronary syndrome and its prognostic value for future cardiovascular events. METHODS: Resistin levels were determined in 1153 patients with stable angina (SAP), 380 patients with unstable angina, 278 patients with non-ST-elevation myocardial infarction (NSTEMI) and 111 patients with ST-elevation myocardial infarction (STEMI). All patients have been followed up for a median follow-up of 2.6 years. During follow-up, 70 patients died from cardiovascular causes. RESULTS: Compared to SAP, resistin levels (5.1 ng/mL in SAP) were elevated in patients with angina at rest (5.89 ng/mL, P=0.001), in patients with NSTEMI (6.00 ng/mL, P<0.001), and in patients with STEMI (5.98 ng/mL, P<0.001). Resistin levels rose at 3-6h after chest pain onset (5.46 ng/mL), persisted elevated among those individuals presenting between 6 and 12h after chest pain onset (5.57 ng/mL) and peaked in individuals presenting more than 12h after chest pain onset (5.74 ng/mL). An increase of one standard deviation of resistin levels was associated with a 1.22-fold (95% CI 1.04-1.43; P=0.02) risk for future fatal cardiovascular events in a model adjusted for risk factors and clinical and therapeutic variables. When adjustment for renal function was applied, this association lost its statistical significance. CONCLUSIONS: Resistin levels are elevated in patients presenting with unstable angina, NSTEMI and STEMI and might play a role as a diagnostic marker. In addition, systemic resistin level is moderately associated with future cardiovascular death in patients with documented coronary artery disease.

Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study.

As a competitive inhibitor of endothelial nitric oxide synthase, asymmetric dimethylarginine (ADMA) has been related to atherosclerotic disease. Little is known about the prognostic impact of baseline ADMA determination. In a prospective cohort of 1908 patients with coronary artery disease, we assessed baseline serum concentration of ADMA in 1874 consecutive patients with coronary artery disease. One hundred fourteen individuals developed the primary end point of death from cardiovascular causes or nonfatal myocardial infarction during a mean follow-up of 2.6+/-1.2 years. Median concentrations of ADMA levels were higher among individuals who subsequently developed the primary end point than among those who did not (0.70 versus 0.63 micromol/L; P<0.001). The risk of future cardiovascular event was associated with increasing thirds of baseline ADMA (P for trend, <0.001) such that individuals in the highest third at entry had a hazard ratio 2.48 times higher than those in the lowest third (95% confidence interval, 1.52 to 4.06; P<0.001). This relationship remained nearly unchanged after adjustment for most potential confounders. Prediction models that simultaneously incorporated ADMA, B-type natriuretic peptide, C-reactive protein, and creatinine in addition to traditional risk factors revealed B-type natriuretic peptide (hazard ratio, 1.96; 95% confidence interval, 1.3 to 3.0; P=0.002) and ADMA (hazard ratio, 1.90; 95% confidence interval, 1.3 to 2.8; P=0.001) as the strongest risk predictors. High levels of baseline ADMA independently predict future cardiovascular risk. ADMA has prognostic value beyond traditional risk factors and novel biomarkers and might guide therapeutic strategies.

Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls - a cross-sectional pilot study.

BACKGROUND: Research has implicated that changes in zinc (Zn) metabolism may be associated with the biological underpinnings of eating disorders, in particular anorexia nervosa. However, to date research on the role of Zn in patients with bulimia nervosa (BN) is scarce. OBJECTIVE: We aimed to explore serum Zn concentrations in young patients with BN, with a focus on the stage of the disorder, comparing acutely ill and recovered patients with BN with healthy controls. METHODS: Serum Zn concentrations were obtained from healthy controls and from acutely ill and remitted young patients with BN. Mean duration of remission was 4.0±3.5 years. RESULTS: Remitted patients showed elevated serum Zn concentrations when compared to controls (Cohen's d=2.022), but concentrations were still in the normal range. Acutely ill patients also had higher serum Zn levels when compared to controls (all values still being within the reference range, Cohen's d=0.882). There was no difference between acutely ill and remitted patients with BN in serum Zn concentrations. Of note, remitted patients had a significantly higher body weight when compared to the other two groups. Overall, there were no significant differences in dietary preferences with regard to Zn containing foods between the groups. CONCLUSION: The present study provides preliminary evidence that the underlying factors for changes in Zn serum concentrations in young patients with BN do not vary with regard to the stage of illness (acute versus remitted BN). Further prospective research is needed in order to disentangle the possible interplay between serum Zn status and bulimic eating behaviors.

Method comparison of cardiac marker assays on PATHFAST, StratusCS, AxSYM, Immulite 2000, triage, elecsys and cardiac reader.

The purpose of this evaluation was to perform a method comparison of the assays for cardiac troponin I (cTnl), CK-MB, myoglobin, and NT-proBNP on the automated PATHFAST Immuno-Assay Analyzer with respective immunoassays on other commercially available immunoanalyzers. The PATHFAST assays are immunochemiluminescent assays (in single reagent cartridges) employing two mono- or polyclonal antibodies in a sandwich test format. The calibration materials for cTnI and CK-MB are standardized to the reference materials NIST SRM 2921 (troponin CIT complex) and IRMM-IFCC 455 (CK-MB mass). The PATHFAST assays for cTnI, CK-MB, myoglobin, and NT-proBNP on the PATHFAST Analyzer were compared using 118 (NT-proBNP: 90) plasma samples from patients with different cardiovascular diseases with those on the Dade Behring StratusCS Analyzer, on the Abbott AxSYM System, on the DPC IMMMULITE 2000 Analyzer, on the Biosite Triage Meter Plus System, on the Roche Elecsys Immuno Analyzer 2010 and Roche Cardiac Reader System, respectively. The correlation coefficients for the comparison of cTnI methods ranged from 0.953 to 0.982, those for the comparison of myoglobin methods ranged from 0.776 to 0.992, and those for the comparison of CK-MB methods ranged from 0.835 to 0.999, with the Triage System giving in all comparisons the lowest correlation. Also the comparison of PATHFAST NTproBNP against the Roche Elecsys assay yielded a very good correlation (r = 0.992). The slopes of the regression line among methods showed considerable variation indicating that standardization efforts by international groups are indispensable to achieve harmonization of results. In summary, this evaluation study confirms the overall good correlation of the results obtained with assays for cardiac markers developed on the PATHFAST analyzer with those on other immunoassay platforms and thus the analytical reliability of the developed methods.