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Biomedical subjects

P Cremer

Publications and source records attributed to P Cremer.

At least 19 recordsLinked to original sources
PubMed2005

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Adult↗
PubMed2001

Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure.

OBJECTIVES: Using a prospective study design, we assessed the value of brain natriuretic peptide (BNP) to identify patients with heart failure who have an increased risk of deterioration of their functional status. Furthermore, we examined the relationship between BNP and various clinical characteristics incorporated into an established survival model used for risk stratification. BACKGROUND: Prediction of the clinical course is a crucial part of the decision-making process about the adequate treatment strategy for patients with advanced congestive heart failure (CHF). Although laborious, multivariable indexes have been established for risk stratification, simple plasma BNP measurements may be as useful as prognostic indicators. METHODS: In 78 patients referred to our heart failure clinic, plasma BNP levels were compared with the results of a multivariable prognostic model. To assess the prognostic power of BNP, the clinical course of this cohort was monitored for a median follow-up period of 398 days. RESULTS: At study entry, plasma BNP and the heart failure survival score (HFSS) showed a significant correlation (r = -0.706). During follow-up, Kaplan-Meier estimates of freedom from clinical events differed significantly for patients above and below the 75th percentile concentrations of plasma BNP (p < 0.0001). Changes in plasma BNP were significantly related to changes in limitations of physical activity, as demonstrated by logistic regression analysis (chi-square statistic = 24.9, p < 0.0001). Proportional hazards analysis confirmed BNP as a powerful predictor of functional status deterioration (p < 0.0001). This prognostic information was as powerful as that derived from the multivariable HFSS. CONCLUSIONS: Measurement of plasma BNP concentrations might provide a useful and cost-effective screening tool that helps reduce the need and frequency for more expensive cardiac tests.

Activities of Daily Living↗
PubMed2000

Creating addressable aqueous microcompartments above solid supported phospholipid bilayers using lithographically patterned poly(dimethylsiloxane) molds

Herein we report the use of microcontact displacement (microCD) to generate addressable arrays of aqueous solutions above fluid lipid bilayers by bringing a patterned PDMS mold into conformal contact with a phospholipid membrane on a solid supported substrate. Epifluorescence microscopy established that the bilayer material was displaced in regions where contact between the mold and substrate was made. Photobleaching experiments confirmed that the bilayer sectors remained individually fluid but completely separated. The microcompartments created by microCD could be individually injected with aqueous solutions that remained sealed from their neighbors. This procedure was then exploited for screening a small library of aqueous-phase molecules for their ability to inhibit binding between surface-bound ligands and soluble protein receptors.

Journal Article↗
PubMed2000

Evaluation of the ADVIA Centaur TSH-3 assay.

An analytical evaluation of the thyroid stimulating hormone (TSH-3) assay on the Bayer ADVIA Centaur immunoassay system was performed. General analytical requirements (linearity, resistance to typical interferences, absence of a carry-over effect) were fulfilled and reproducibility was satisfactory. Inter-assay coefficient of variation (CV) of a human serum pool with a concentration of 0.014 mU/l was 22.3%; at concentrations between 0.26 and 83 mU/l CV was below 6%. Method comparison study demonstrated close agreement of TSH results compared to those obtained with the Roche Elecsys 2010 TSH assay (ADVIA Centaur = 1.08 x Elecsys - 0.18 mU/l; r=0.987; n=324). Handling and practicability of the ADVIA Centaur system proved to be convenient with a very high sample throughput. We conclude that the ADVIA Centaur TSH-3 assay meets requirements for clinical use.

Humans↗
PubMed2000

Therapeutic drug monitoring on COBAS INTEGRA 400--evaluation results.

The COBAS INTEGRA 400 (Roche Diagnostics GmbH) is a random access analyzer with a consolidated test menue for routine clinical chemistry, specific proteins, drugs of abuse screening and therapeutic drug monitoring (TDM) and different measuring technologies. It was the aim of the present study to evaluate the suitability of this instrument as dedicated analyzer for TDM. Eight assays based on three different technologies were included: Acetaminophen (enzymatic method), Amikacin/ Phenytoin/ Free Phenytoin/ Lidocaine (fluorescence polarization immunoassays; FPIA), Digitoxin/Digoxin (kinetic interaction of microparticles in solution; KIMS). The study comprised the determination of imprecision according to NCCLS EP-T protocol, method comparison and linearity studies. The assays were compared with the corresponding methods on AxSYM or TDx analyzers (Abbott Laboratories). For Acetaminophen and Amikacin COBAS INTEGRA 700 was used as additional comparison instrument. The results are summarized in a table (table 6). Precision results are well acceptable with within-run CVs < 5% and total CVs < 6% except for Digitoxin and Digoxin which show a somewhat higher imprecision at low concentrations. Results obtained for Acetaminophen and Amikacin on COBAS INTEGRA 400 and 700 show excellent agreement. A good comparability is also found between COBAS INTEGRA 400 and AxSYM or TDx methods with slight systematic deviations for Acetaminophen, Amikacin and Free Phenytoin. The lower correlation coefficient for the digoxin method comparison can be attributed to two discrepant samples. Linearity throughout the range studied which covered > 80% of the measuring range was confirmed for the five assays tested (Digitoxin, Digoxin, Lidocaine, Free Phenytoin, Phenytoin) based on the acceptance criteria of +/- 10% deviation of the measured values from the theoretical values. Based on the analytical performance of the TDM tests studied it can be concluded that the COBAS INTEGRA 400 is very well suited for routine TDM analysis.

Drug Monitoring↗
PubMed1998

Association of serum tumor necrosis factor levels with decrease of cholesterol during septic shock.

Recent studies suggest that release of cytokines during inflammatory states such as septic shock leads to hypocholesterolemia. To examine whether tumor necrosis factor alpha (TNF), which is the major cytokine in inflammatory disease, causes hypocholesterolemia, we measured serum levels of total (bioactive and receptor-bound) TNF, cholesterol, Apo B, and Apo A1 in seven patients with septic shock over a period of 8 days. Since elevated serum TNF levels are accompanied by the release of soluble TNF receptors, levels of TNF receptors p55 and p75 were also measured. Patients with septic shock had significantly higher serum TNF and TNF receptor levels compared with healthy controls. Increased cytokine levels were accompanied by a significant decline in total serum cholesterol apolipoprotein A1 and B. In vitro studies with cultured human skin fibroblasts, human umbilical vein endothelial cells, and HepG2 hepatoma cells showed that TNF increased the degradation of 125I-labeled low-density lipoprotein in all the cell lines tested. Recombinant soluble TNF receptors inhibited the TNF-induced stimulation of low-density lipoprotein receptor in a concentration-dependent manner. However, the calculated ratio of TNF receptors to total TNF measured in serum of these patients was not able to counteract the stimulatory effect of TNF, possibly due to the higher molar excess of TNF receptors required to achieve this effect in vitro. Our data strengthen the hypothesis that serum values of total TNF determine the extent of hypocholesterolemia during sepsis and septic shock despite the presence of a high concentration of TNF receptors. Studies with recombinant TNF also confirm the role of TNF in hypocholesterolemia in inflammation.

Aged↗
PubMed1998

Validation of an automated enzyme immunoassay for Interleukin-6 for routine clinical use.

Serum levels of Interleukin-6 (IL-6), a proinflammatory cytokine, are increased in early stages of inflammatory diseases such as infection and sepsis. Assay systems which permit its measurement within a few hours and as a single measurement have not been reported so far. We therefore evaluated a now commercially available automated method for IL-6 measurement on the Cobas Core immunological analyzer (Roche Diagnostic Systems) which enables single IL-6 measurement within about 1 hour. The automated assay correlates well with an established, manual microtiter plate assay (Biosource GmbH) which uses the same antibodies and reagents (r=0.98). Accuracy of the automated method was established by adding known amounts of IL-6 international reference preparation. Recovery of the international standard was in the range of 92104%. The automated assay had a precision of singletons below 6% and was linear up to 2800 pg/ml. This automated assay provides a suitable, convenient and time saving method for measurement of IL-6 serum levels in the routine clinical laboratory.

Automation↗
PubMed1998

Reference standardization and triglyceride interference of a new homogeneous HDL-cholesterol assay compared with a former chemical precipitation assay.

A homogeneous HDL-c assay (HDL-H), which uses polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin, was assessed for precision, accuracy, and cholesterol and triglyceride interference. In addition, its analytical performance was compared with that of a phosphotungstic acid (PTA)/MgCl2 precipitation method (HDL-P). Within-run CVs were < or = 1.87%; total CVs were < or = 3.08%. Accuracy was evaluated in fresh normotriglyceridemic sera using the Designated Comparison Method (HDL-H = 1.037 Designated Comparison Method + 4 mg/L; n = 63) and in moderately hypertriglyceridemic sera by using the Reference Method (HDL-H = 1.068 Reference Method - 17 mg/L; n = 41). Mean biases were 4.5% and 2.2%, respectively. In hypertriglyceridemic sera (n = 85), HDL-H concentrations were increasingly positively biased with increasing triglyceride concentrations. The method comparison between HDL-H and HDL-P yielded the following equation: HDL-H = 1.037 HDL-P + 15 mg/L; n = 478. We conclude that HDL-H amply meets the 1998 NCEP recommendations for total error; its precision is superior compared with that of HDL-P, and its average bias remains below +/-5% as long as triglyceride concentrations are < or = 10 g/L and in case of moderate hypercholesterolemia.

Chemical Precipitation↗
PubMed1998

Elecsys CEA, PSA and AFP. Clinical results of a multicentre evaluation.

Three tumormarker assays, Elecsys CEA, PSA and AFP, have been evaluated in an international multicentre study to characterize their clinical performance and to verify the comparability with the corresponding tests of the Enzymun-Test product line and other methods. For each of the markers results were obtained from four laboratories. On the basis of 314 and 199 specimens respectively, (preliminary) reference ranges could be established for CEA and PSA. For the prostate marker, the age dependence of the antigen level could be clearly confirmed. Mean concentrations range between 0.51 ng/ml (< 40 years) and 3.57 ng/ml (> 70 years). Referring to CEA, 95th percentiles of 4.31 ng/ml and 2.69 ng/ml were elaborated for smokers and nonsmokers. In general, good to excellent correlations (r > 0.98) were found between the Elecsys and Enzymun-Tests. Regarding the systematic comparability of both systems, most of the slopes derived from the individual method comparison studies are within the +/- 10% range of the respective standardization results. The specific distribution pattern of the individual tumormarker values elaborated with sample material of known clinical background, reflects the well established categorization of different benign and malignant diseases according to their characteristic marker levels. Of utmost importance, however, is the excellent comparability of the Elecsys assays with the corresponding Enzymun-Tests and the FDA approved AIA 1200 tests from TOSOH in follow-up studies. Almost superimposable concentration curves guarantee that identical diagnostic information is derived from all three methods. Especially for PSA, a series of measurements on sera of prostatectomized patients proved the usability and clinical value of the test also for this particular indication. For either one of the Elecsys tests, the feasibility of using plasma as sample material was verified.

Adult↗
PubMed1997

Ten-year follow-up results from the Goettingen Risk, Incidence and Prevalence Study (GRIPS). I. Risk factors for myocardial infarction in a cohort of 5790 men.

Besides the accepted major risk factors for myocardial infarction (MI), cholesterol, hypertension and smoking, several other variables such as lipoproteins, apolipoproteins, fibrinogen and family history of MI, have been considered, but their usefulness as predictors of MI is controversially discussed. The Göttingen Risk Incidence and Prevalence Study (GRIPS) aimed to evaluate the independent impact of the latter in comparison to the established risk factors. GRIPS is a prospective cohort study, which included 5790 men, aged 40-59.9 years, without cardiovascular disease at baseline. Multivariate logistic regression models for the estimation of the MI risk based on the 10-year follow-up data from 97.4% of the study participants established LDL cholesterol as the strongest predictor of MI. It was followed by family history of MI, Lp(a), age, smoking, systolic blood pressure, HDL cholesterol (inversely related) and plasma glucose (P < 0.001). Apolipoprotein B as well as the ratios total/HDL cholesterol, LDL/HDL cholesterol and Apo B/AI were less effective predictors than LDL cholesterol and did not contribute independently to the estimation of MI risk. Similarly apoprotein AI was a weaker predictor of MI risk then HDL cholesterol. GRIPS is the first prospective cohort study which clearly justifies the key role of LDL cholesterol in preventive strategies. However, the data also give strong support for the additional consideration of other risk factors for a valid estimation of the MI risk for an individual subject.

Blood Glucose↗
PubMed1997

Chronic work stress is associated with atherogenic lipids and elevated fibrinogen in middle-aged men.

OBJECTIVES: To examine the association between a model of chronic work stress (high efforts in combination with low rewards) and two risk factors of coronary heart disease, low-density-lipoprotein (LDL)-cholesterol and fibrinogen. DESIGN: A cross-sectional study in a group of 179 healthy middle-aged (48.5 +/- 4.5) male middle managers. SETTING: A large car-producing enterprise in Germany. RESULTS: After adjustment for relevant covariates, logistic regression analysis showed independent effects of a composite measure of high effort and low reward at work on the prevalence of elevated (upper tertile, i.e. > or = 160 mg dL-1) LDL-cholesterol (prevalence odds ratio (POR) = 3.57; 95% confidence intervals (CI): 1.24-10.20) and on elevated (upper quintile, i.e. > or = 420 mg dL-1) plasma fibrinogen (POR = 6.71 (CI: 1.57-28.76). Apart from this core measure, cigarette smoking, overweight and alcohol consumption were the covariates with the relatively strongest contributions to the multivariate model. CONCLUSIONS: Results give preliminary evidence on an independent association of chronic work stress with atherogenic lipids and with elevated fibrinogen in an occupationally homogeneous group of healthy middle-aged men.

Adult↗
PubMed1997

Increased oxidation of LDL in patients with coronary artery disease is independent from dietary vitamins E and C.

There is increasing experimental evidence that oxidation of LDL plays a major role in the pathogenesis of coronary artery disease (CAD). However, results from clinical studies on LDL oxidation and CAD are not consistent. In most studies only single plasma factors of LDL oxidation have been determined. We studied 207 patients who underwent coronary angiography. They were divided into subjects with CAD (n = 137) and those without CAD (n = 70). We determined the susceptibility of LDL to in vitro oxidation (lag phase), potential prooxidative and antioxidative plasma factors (plasma vitamin E, LDL vitamin E, ascorbate, iron, copper, ferritin, and ceruloplasmin), and markers of in vivo LDL oxidation (autoantibodies to malondialdehyde-modified LDL, oxidized LDL, and thiobarbituric acid-reactive substances), plasma lipids and lipoproteins, smoking habits, and other coronary risk factors in both groups. The lag phase was significantly shorter in patients with CAD than in patients without CAD (101 +/- 38.6 versus 119 +/- 40.6 minutes, P < .01). There was no correlation between the lag phase and the other oxidation parameters or the coronary risk factors. In multivariate regression analyses the lag phase remained significant in all tested models. Our data suggest that a short lag phase of LDL oxidation might be an independent risk factor of CAD.

Aged↗