Background The Model for End Stage Liver Disease (MELD) score is utilized as a prognostic tool for end-stage liver disease. The variations in laboratory tests have a substantial impact on MELD. For creatinine as one parameter in the MELD score, measurements are mostly performed by either Jaffé kinetic or enzymatic assays. In both assays, bilirubin is recognized to significantly interfere with the creatinine detection.

Introduction Diurnal biological rhythms may have an influence on laboratory diagnostics and could affect assessment of disease state. However, the extent of variation due to biological rhythms is unknown for most parameters with clinical relevance.

Prehypertension is a frequent condition and has been demonstrated to increase cardiovascular risk. However, the association with coronary atherosclerosis as part of target organ damage is not well understood. We investigated the cross-sectional relationship and longitudinal outcome between blood pressure categories and coronary artery calcification (CAC), quantified by electron beam computed tomography, in 4181 participants from the population-based Heinz Nixdorf Recall Study cohort. At baseline, we observed a continuous increase in calcium scores with increasing blood pressure categories. During a median follow-up period of 7.18 years, 115 primary end points (2.8%; fatal and nonfatal myocardial infarction) and 152 secondary end points (3.6%; stroke and coronary revascularization) occurred. We observed a continuous increase in age- and risk factor-adjusted secondary endpoints (hazard ratios [95% CI]) with increasing blood pressure categories (referent: normotension) in men: prehypertension, 1.80 (0.53–6.13); stage 1 hypertension, 2.27 (0.66–7.81); and stage 2 hypertension, 4.10 (1.27–13.24) and in women: prehypertension, 1.13 (0.34–3.74); stage 1 hypertension, 2.14 (0.67–6.85); and stage 2 hypertension, 3.33 (1.24–8.90), respectively, but not in primary endpoints. Cumulative event rates were determined by blood pressure categories and the CAC. In prehypertension, the adjusted hazard ratios for all of the events were, for CAC 1 to 99, 2.05 (0.80–5.23; P =0.13); 100 to 399, 3.12 (1.10–8.85; P =0.03); and ≥400, 7.72 (2.67–22.27; P =0.0002). Risk of myocardial infarction and stroke in hypertension but also in prehypertension depends on the degree of CAC. This marker of target-organ damage might be included, when lifestyle modification and pharmacotherapeutic effects in prehypertensive individuals are tested to avoid exposure to risk and increase benefit.

Various models are used for investigating human liver diseases and testing new drugs. However, data generated in such models have only limited relevance for in vivo conditions in humans. We present here an ex vivo perfusion system using human liver samples that enables the characterization of parameters in a functionally intact tissue context. Resected samples of noncirrhotic liver (NC; n = 10) and cirrhotic liver (CL; n = 12) were perfused for 6-h periods. General and liver-specific parameters (glucose, lactate, oxygen, albumin, urea, and bile acids), liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glutamate dehydrogenase, and γ-glutamyl transferase), overall (M65) and apoptotic (M30) cell-death markers, and indicators of phase-I/phase-II biotransformations were analyzed. The measurement readings closely resembled (patho)physiological characteristics in patients with NC and CL. Mean courses of glucose levels reflected the CLs' reduced glycogen storage capability. Furthermore, CL samples exhibited significantly stronger increases in lactate, bile acids, and the M30/M65 ratio than NC specimens. Likewise, NC samples exhibited more rapid phase-I transformations of phenacetin, midazolam, and diclofenac and phase-I to phase-II turnover rates of the respective intermediates than CL tissue. Collectively, these findings reveal the better hepatic functionality in NC. Perfusion of human liver tissue with this system emulates in vivo conditions and clearly discriminates between noncirrhotic and cirrhotic tissue. This highly reliable device for investigating basic hepatic functionality and testing safety/toxicity, pharmacokinetics/pharmacodynamics and efficacies of novel therapeutic modalities promises to generate superior data compared with those obtained via existing economic perfusion systems.

Background and Aims: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor condition leading to hematological malignancies. An association of MGUS with inflammatory disorders was reported. As particulate matter (PM) can induce chronic inflammation, we asked whether there is an association of PM exposure and MGUS. Methods: We screened baseline and 5-year follow-up serum samples of the Heinz Nixdorf Recall Study, an ongoing cohort study of 4,814 participants aged 45-75 years in Germany. Serum electrophoresis and immunofixation (Hydragel 12 IF, Penta-Kit, Sebia, Fulda, Germany) was used to detect MGUS. The individual one-year average PM2.5 and PM10 exposure prior to baseline was assessed using a dispersion and chemistry transport model (EURAD). We calculated distance from participants' home addresses to highly trafficked roads. PM values were categorized in quartiles. Poisson regression was used to model incident MGUS adjusting for sex and age. Logistic regression was used to calculate odds ratios (OR) for prevalent MGUS at follow-up adjusted for distance, age, sex, BMI, education, smoking status, and physical activity. Results: At baseline 165 MGUS cases were identified among 4,702 screened participants (prevalence 3.5%, 95%-CI 3.0-4.1). Among 3,862 participants free of disease at baseline, 50 (1.3%) new MGUS were identified. Median one-year PM2.5 and PM10 concentrations were 16.6μg/m³ (IQR 2.4) and 20.7μg/m³ (IQR 4.0), respectively. Age-and sex-adjusted relative risk of incident MGUS in increasing quartiles of PM2.5 exposure was 2.78 (95%-CI 1.09-7.11), 1.58 (0.56-4.44), and 3.33 (1.33-8.34), respectively. Fully adjusted ORs for prevalence of MGUS at follow-up in increasing quartiles of PM2.5 were 1.02 (0.65-1.62), 0.98 (0.62-1.56), and 1.54 (1.02-2.34). Effect estimates for PM10 showed a positive trend. Conclusions: We provide first data suggesting that residential exposure to particulate matter may increase risk of MGUS and thus linking chronic particle exposure with cells of the adaptive immune system.

INTRODUCTION:Established biomarkers for the diagnosis of sepsis are procalcitonin, interleukin 6, and C-reactive protein. Although sepsis evokes changes of coagulation and fibrinolysis, it is unknown whether thromboelastometry can detect these alterations. We investigated whether thromboelastometry variables are suitable as biomarkers for severe sepsis in critically ill adults. METHODS:In the observational cohort study, blood samples were obtained from patients on the day of diagnosis of severe sepsis (n = 56) and from postoperative patients (n = 52), and clotting time, clot formation time, maximum clot firmness, alpha angle, and lysis index were measured with thromboelastometry. In addition, procalcitonin, interleukin 6, and C-reactive protein levels were determined. For comparison of biomarkers, receiver operating characteristic (ROC) curves were used, and the optimal cut-offs and odds ratios were calculated. RESULTS:In comparison with postoperative controls, patients with sepsis showed an increase in lysis index (97% ± 0.3 versus 92 ± 0.5; P < 0.001; mean and SEM) and procalcitonin (2.5 ng/ml ± 0.5 versus 30.6 ± 8.7; P < 0.001). Clot-formation time, alpha angle, maximum clot firmness, as well as interleukin 6 and C-reactive protein concentrations were not different between groups; clotting time was slightly prolonged. ROC analysis demonstrated an area under the curve (AUC) of 0.901 (CI 0.838-0.964) for the lysis index, and 0.756 (CI 0.666-0.846) for procalcitonin. The calculated cut-off for the lysis index was > 96.5%, resulting in a sensitivity of 84.2%, and a specificity of 94.2%, with an odds ratio of 85.3 (CI 21.7-334.5). CONCLUSIONS:The thromboelastometry lysis index proved to be a more reliable biomarker of severe sepsis in critically ill adults than were procalcitonin, interleukin 6, and C-reactive protein. The results also demonstrate that early involvement of the hemostatic system is a common event in severe sepsis.

High-density lipoproteins (HDL) are the major plasma carriers for sphingosine 1-phosphate (S1P) in healthy individuals, but their S1P content is unknown for patients with coronary artery disease (CAD). The aim of the study was to determine whether the S1P levels in plasma and HDL are altered in coronary artery disease. S1P was determined in plasma and HDL isolated by ultracentrifugation from patients with myocardial infarction (MI, n = 83), stable CAD (sCAD, n = 95), and controls (n = 85). In our study, total plasma S1P levels were lower in sCAD than in controls (305 vs. 350 pmol/mL). However, normalization to HDL-cholesterol (a known determinant of plasma S1P) revealed higher normalized plasma S1P levels in sCAD than in controls (725 vs. 542 pmol/mg) and even higher ones in MI (902 pmol/mg). The S1P amount contained in isolated HDL from these individuals was lower in sCAD than in controls (S1P per protein in HDL: 132 vs. 153 pmol/mg). The amount of total plasma S1P bound to HDL was lower in sCAD and MI than in controls (sCAD: 204, MI: 222, controls: 335 pmol/mL), while the non-HDL-bound S1P was, accordingly, higher (sCAD: 84, MI: 81, controls: 10 pmol/mL). HDL-bound plasma S1P was dependent on the plasma HDL-C in all groups, but normalization to HDL-C still yielded lower HDL-bound plasma S1P in patients with sCAD than in controls (465 vs. 523 pmol/mg). The ratio of non-HDL-bound plasma S1P to HDL-C-normalized HDL-bound S1P was also higher in both sCAD (0.18 mg/mL) and MI (0.15 mg/mL) than in controls (0.02 mg/mL). Remarkably, levels of non-HDL-bound plasma S1P correlated with the severity of CAD symptoms as graded by Canadian Cardiovascular Score, and discriminated patients with MI and sCAD from controls. Furthermore, a negative association was present between non-HDL-bound plasma S1P and the S1P content of isolated HDL in controls, but was absent in sCAD and MI. Finally, MI patients with symptom duration of less than 12 h had the highest levels of total and normalized plasma S1P, as well as the highest levels of S1P in isolated HDL. The HDL-C-normalized plasma level of S1P is increased in sCAD and even further in MI. This may be caused by an uptake defect of HDL for plasma S1P in CAD, and may represent a novel marker of HDL dysfunction.

Daily to monthly variations in fine particulate matter have been linked to systemic inflammatory responses. It has been hypothesized that smaller particles resulting from combustion processes confer higher toxicity. We aim to analyze the association between short-term exposure to ultrafine and fine particles and systemic inflammation. We use baseline data (2000–2003) of the Heinz Nixdorf Recall Study, a population-based cohort study of 4,814 participants in the Ruhr Area in Germany. A chemistry transport model was applied to model daily surface concentrations of particulate air pollutants on a grid of 1 km 2 . Exposure included particle number (PN) and particulate matter mass concentration with an aerodynamic diameter ≤2.5 μm (PM 2.5 ) and ≤10 μm (PM 10 ). Generalized additive models were used to explore the relation of air pollutants using single day lags and averaging times of up to 28 days with high-sensitivity C-reactive protein (hs-CRP). We adjusted for meteorology, season, time trend, and personal characteristics. Median hs-CRP level in the 3,999 included participants was 1.5 mg/l. Median daily concentration of PN was 8,414 × 10 4 /ml (IQR 4,580 × 10 4 /ml), of PM 2.5 14.5 μg/m³ (IQR 11.5 μg/m³) and of PM 10 18.5 μg/m³ (IQR 13.9 μg/m³). A positive association between PN and hs-CRP could be observed only for single day lags and for averaged PN concentrations with higher estimates for longer averaging times. The highest hs-CRP-increase of 7.1% (95%-CI: 1.9, 12.6%) was found for the 21-day average. These results support the hypothesis that short-term exposure to traffic-related particles might lead to detrimental cardiovascular health effects via an inflammatory mechanism.

Exercise capacity and heart rate profile parameters obtained from exercise stress testing as well as the subclinical coronary atherosclerosis burden from cardiac CT have been suggested to improve cardiovascular (CV) risk stratification beyond traditional risk factors (RF) in persons at risk of CV events.

The Eastern Ghat Mobile Belt (EGMB), a tectonically active area extends along the eastern margin of Peninsular India, is divided into three provinces, namely, Eastern Ghat Province, the Jeypore Province, and the Krishna Province. The Ongole domain of Krishna Province is a seismically active region that has experienced four moderate earthquakes of magnitude ⩾5.0, of which largest one is of magnitude 5.4 occurred on 27th March 1967. The crustal shear wave velocity structure in the Eastern Ghat Mobile Belt has been investigated using joint inversion of receiver functions and Rayleigh wave group velocity at 5 locations in the study region. The results show crustal thickness variation from 37 to 42 km and average shear velocity variation from 3.67 to 3.78 km/s in the study region. A low velocity layer of variable thickness and velocities 3.54–3.7 km/s) is also observed in the region. The low velocity layer in most of the stations is observed at a depth of ∼20 km. This low velocity layer may be due to the presence of fluid in the crust, which also be one of the causes of the intraplate earthquakes in the study region.

Das größte Potenzial zur Verhinderung von Herzinfarkt und plötzlichem Herztod liegt bei der Prävention und Gesundheitsförderung. Die derzeitigen Algorithmen zur individuellen KHK-Risikostratifikation beschreiben das Risiko nur ungenau. Die Heinz Nixdorf Recall Studie ist eine bevölkerungsbasierte, prospektive Kohortenstudie, die seit 2000 im Ruhrgebiet durchgeführt wird. Primäres Ziel ist eine verbesserte Vorhersage kardiovaskulärer Ereignisse mit Schwerpunkt auf die Evaluation der prognostischen Bedeutung der koronaren Kalzifizierung (CAC). Durch die nichtinvasive Quantifizierung des Koronarkalks könnte die individuelle Arteriosklerosedynamik durch oftsubklinisch verlaufende Plaquerupturen erkannt werden, lange bevor ein unumkehrbares klinisches Ereignis eintritt. Weitere Ziele liegen in der Untersuchung der Wirkung psychosozialer Risikofaktoren, Umweltfaktoren oder genetischer Einflussgrößen auf die CAC-Progression und KHK-Ereignisse.

We carried out a genome-wide association study in 296 individuals with male-pattern baldness (androgenetic alopecia) and 347 controls. We then investigated the 30 best SNPs in an independent replication sample and found highly significant association for five SNPs on chromosome 20p11 (rs2180439 combined P = 2.7 x 10(-15)). No interaction was detected with the X-chromosomal androgen receptor locus, suggesting that the 20p11 locus has a role in a yet-to-be-identified androgen-independent pathway.

Objectives: The ratio of the urinary mass concentrations of cystatin C and creatinine (UcysC/Ucrea)>= 11.3 mg/mmol has recently been proposed as an accurate marker for the detection of GFR <= 60 mL/min/1.73 m(2).Design and methods: We prospectively evaluated the diagnostic performance of UcysC/Ucrea >= 11.3 mg/mmol and factors associated with increased UcysC/Ucrea in 72 children and adults with a wide variety of renal disorders. UcysC/Ucrea was calculated, and GFR wad estimated from serum creatinine and cystatin C by equations.Results: UcysC/Ucrea >= 11.3 mg/mmol had a low diagnostic value to detect GFR values <= 60 mL/min/1.73 m(2) estimated by creatinine or cystatin-C-based equations with sensitivities of 72% and 63%, and specificities of 42% and 34%. ROC curves for UcysC/Ucrea to detect GFR: 60 mL/min/1.73 in 2 confirmed this with AUCs of 0.59 for creatinine and 0.57 for eystatin-C-based equations. Multivariate analysis identified tubular proteinuria, tubutointerstitial disease and heavy proteinuria, but not GFR <= 60 mL/min/1.73 m(2), as factors independently associated with increased UcysC/Ucrea.Conclusions: UcysC/Ucrea >= 11.3 mg/mmol is not an accurate marker to detect GFR <= 60 mL/min/1.73 m(2), but reflects tubular dysfunction and proteinuria due to heavy proteinuria and tubulointerstitial disease. (c) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Die Heinz Nixdorf Recall Studie ist eine seit dem Jahr 2000 laufende bevölkerungsbasierte Studie zur verbesserten Vorhersage kardiovaskulärer Ereignisse durch Einbeziehung moderner bildgebender und nichtbildgebender Verfahren. Ein Schwerpunkt liegt in der Evaluation der prognostischen Bedeutung der koronaren Kalzifizierung („coronary artery calcium“ [CAC]).

Background: Regular physical exercise is recommended to reduce cardiovascular mortality. And yet, atherosclerosis is the main cause of exercise-associated death in persons beyond age 35. The need for risk stratification in marathon runners is under discussion. The predictive value of modern imaging- and non-imaging-based markers of risk that can be used for risk stratification in masters endurance athletes still deserves exploration.Methods: Male runners > 50 years who have completed at least five marathon races during the preceding 3 years and do not suffer from coronary artery disease, angina nor diabetes mellitus are studied to assess the predictive value of established and modern imaging-based and biochemical cardiovascular risk factors. Laboratory parameters including clinical chemistry, hematology and hormone measurements are determined. Lifestyle-related risk factors, psychosocial and socioeconomic variables are explored using standardized questionnaires. Coronary, carotid, femoral and aortic atherosclerosis is measured using electron-beam computed tomography and ultrasound. In addition, a resting ECG, a bicycle stress test and heart rate variability are performed. Myocardial morphology and function are assessed using echocardiography and magnetic resonance imaging. Participants are invited to compete in a marathon race to quantify the association of coronary atherosclerosis with marathon-related changes of cardiac troponin levels and the extent of marathon-induced inflammation. At the cellular level, the effect on the amount of circulating progenitor cells (EPCs) is determined by FACS analysis. Changes in laboratory parameters and hormone levels are also studied. Annual long-term follow-up including hospital records and death certificates is performed. Data are compared with those from a general unselected cohort from the Heinz Nixdorf Recall Study.Conclusion: This study should contribute to cardiovascular risk assessment in the growing number of masters marathon runners with a focus on assessing the predictive value of modern imaging techniques and biochemical markers for comprehensive risk stratification.

Das Schilddrusenkarzinom ist die am weitesten verbreitete bosartige endokrine Veranderung. Zwar haben vielen Patienten gute Heilungschancen, jedoch sind die Prognosen fur etwa zehn Prozent der Betroffenen sehr schlecht, da Chemotherapie und Bestrahlung nur geringfugigen Einfluss auf Schilddrusenkarzinome nehmen konnen. Neue Therapien, wie sie auch in Essen erforscht werden, setzen auf molekularer Ebene im Stoffwechsel der Zellen an.