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Biomedical subjects

Werner Wosniok

Publications and source records attributed to Werner Wosniok.

12 recordsLinked to original sources
PubMed2006

Liver histopathology in Baltic flounder (Platichthys flesus) as indicator of biological effects of contaminants.

Results are presented of a study on liver histopathology in Baltic flounder (Platichthys flesus) carried out in 2001 and 2002 in four coastal sampling areas of the Baltic Sea: Kvädöfjärden (Swedish east coast, reference area), Klaipeda-Butinge (Lithuanian coast), Gulf of Gdansk (Polish coast), and Wismar Bay (German coast) within the framework of the EU-funded BEEP project. Liver lesions were diagnosed and categorised using standardised methodologies and, for a spatial and temporal assessment of the prevalence and types of lesions detected, a scoring system was applied, involving the calculation of mean histopathology lesion scores. 83.0% of the 436 female flounder examined (size range: 20-43 cm total length, age range: 2-8 years) were affected by liver lesions, out of which 74.3% were assigned to the category of non-specific, 3.4% to the category of early toxicopathic non-neoplastic, 4.6% to the category of pre-neoplastic and 0.7% to the category of neoplastic lesions. Mean lesions scores were highest in the areas at the Lithuanian and Swedish coast and there is indication of an impact of the age structure of the flounder populations studied, the sampling season as well as of contaminant effects.

Age Factors↗
PubMed2006

Comparability of indices for insulin resistance and insulin secretion determined during oral glucose tolerance tests.

BACKGROUND: Impaired insulin secretion (IS) and insulin resistance (IR) play an essential role in the pathogenesis of type 2 diabetes mellitus. Several simplifying indices were developed that calculate IS and/or IR from venous insulin and glucose concentrations. The aim of the present study was to compare these indices with each other and with regard to their efficiency to differentiate between non-diseased and diabetic glucose tolerance states. METHODS: Oral glucose tolerance tests were performed in 301 subjects. The study group was divided into five groups according to WHO/American Diabetes Association (ADA) cut-off values: apparently normotolerant, diabetic, isolated 2-h post-challenge hyperglycemic, isolated fasting hyperglycemic and intermediate groups. The minimal error rate (diagnostic non-efficiency) indicating a misclassification of a diabetic tolerance state was determined for 12 indices. RESULTS: The error rate was lower than 15% for the index of Cederholm and Wibell and for the indices of Stumvoll et al. The misclassification rates for the other indices (index of Matsuda and de Fronzo, index of Myllynen et al., HOMA IR, HOMA beta-cell, FIRI, QUICKI, index of McAuley and insulinogenic index) were 20-27%; however, the diagnostic sensitivity was close to a 1:1 chance of a correct decision. The hypothesis that isolated post-prandial hyperglycemia (IPH) and isolated fasting hyperglycemia (IFH) differ in their insulin sensitivity and insulin response could not be supported by the present results. CONCLUSIONS: The indices of Cederholm and Wibell and of Stumvoll et al. were found to be appropriate as diagnostic indicators of the pathogenesis of diabetic glucose tolerance and were more closely related to the glucose tolerance state than the other indices.

Administration, Oral↗
PubMed2006

Prevalence-dependent decision limits for the early detection of type 2 diabetes mellitus in venous blood, venous plasma and capillary blood during glucose challenge.

BACKGROUND: The glycemia decision limits recommended by WHO/ADA for type 2 diabetes detection are derived from clinical signs in advanced stages of the disease. Since insulin secretion patterns and sensitivitity are impaired at the beginning of type 2 diabetes, this stage may be better suited to identify decision limits with higher diagnostic efficiency than those currently applied. METHODS: Oral glucose tolerance tests were performed in 300 subjects. Glucose concentrations were measured at 30-min intervals in venous plasma, venous blood and capillary blood. Insulin concentrations in venous plasma, an insulin sensitivity index and body mass index were used to indicate a type 2 diabetic state. A multiple logistic regression procedure was "trained" using only subjects "clearly" considered to be non-diseased or diseased based on an oral glucose tolerance test according to WHO criteria. This insulin algorithm was applied to the whole study group, leading to definitive classification into the non-diseased or the diseased group. This a posteriori classification was used to identify cutoff values with the highest diagnostic efficiency. RESULTS: The diagnostic efficiency was significantly higher when decision limits lower than the WHO recommendations for glucose concentrations were applied in a preselected subpopulation and in all three sample systems tested, e.g., 9.49 mmol/L (171 mg/dL) for venous plasma and 8.94 mmol/L (161 mg/dL) for capillary blood in the 2-h post-load state. The optimized and WHO 2-h cutoff values corresponded to a disease prevalence of 28% and approximately 5% (20% in the fasting state), respectively. Diagnostic efficiency was higher in the 2-h post-load than in the fasting state. Combining fasting values with 2-h post-load values did not further improve the diagnostic efficiency. Glucose concentrations determined from capillary blood were as efficient as those from venous blood or plasma. The number of diabetic subjects detected differed considerably between capillary blood and venous plasma for the WHO/ADA cutoff values, but not for the optimized cutoff values. CONCLUSIONS: The efficiency of type 2 diabetes diagnosis can be improved by optimizing cutoff values according to disease prevalence. Unexpectedly, the optimized 2-h post-load cutoff was lower for capillary blood than for venous plasma. It is proposed to identify a risk group e.g., by characteristics of the metabolic syndrome in which the 2-h post-challenge concentration is determined using lower cut-off values than presently recommended.

Adult↗
PubMed2005

Ethoxyresorufin-O-deethylase (EROD) activity in dab (Limanda limanda) as biomarker for marine monitoring.

GOAL, SCOPE AND BACKGROUND: Ethoxyresorufin-O-deethylase (EROD) is a well-accepted marker for biological effects in fish and is, therefore, part of numerous monitoring programmes. EROD activity was measured in livers of dab (Limanda limanda) from the German Bight (North Sea) from 1995 to 2003. The aim of the present long-term study was (a) time trend monitoring of EROD activity of dab from the German Bight and (b) to elucidate the needs for a successful application of EROD activity as an early warning system. METHODS: EROD activities were determined fluorimetrically in dab liver microsomes, using resorufin as an external standard. The limit of detection (LD) and the limit of quantification (LQ) were calculated. Results were referred to protein concentrations. RESULTS AND DISCUSSION: EROD activities of 610 female dab caught in different seasons between January 1995 and August 2003 were analyzed individually. Activities varied from < LD to 1768 pmol/(min mg protein) and showed an annual cycle as well as significant differences between the years. Highest EROD activities were observed in early summer and lowest activities during the winter period. In autumn 2002, significantly elevated EROD activities were detected, possibly related to effects of the River Elbe flood event. Two scenarios with different EROD baseline data are presented to discuss the prerequisites for the use of EROD as a monitoring tool. The comparison of these scenarios underlines the importance of appropriate season-specific baseline data. CONCLUSION: The use of EROD as an early warning tool for contaminant effects in dab in the German Bight has different prospects during the year, because, due to the high background variability, elevated EROD activities are less easy to detect in spring/ summer than during the remaining times of the year. RECOMMENDATION AND OUTLOOK: The availability of site-specific data on the EROD baseline level, its random variation and its annual cycle is a necessary prerequisite for monitoring. If monitoring is to be carried out only for a limited time period of the year, a season with low background variability in EROD activity (autumn) should be chosen to avoid the need for a compensation of the temperature-triggered shift in sexual cycles and the resulting changes in EROD activity.

Animals↗
PubMed2004

Genotoxic and teratogenic potential of marine sediment extracts investigated with comet assay and zebrafish test.

Organic extracts of marine sediments from the North Sea and the Baltic Sea were investigated with two toxicity assays. The comet assay based on the fish cell line Epithelioma papulosum cyprini (EPC) was applied to determine the genotoxic potential; zebrafish embryos (Danio rerio) were used to quantify the teratogenic potential of the samples. EC(50) values were calculated from dose-response curves for both test systems. Highest teratogenic and genotoxic effects normalised to total organic carbon (TOC) content were detected in sediment samples of different origins. Polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) are not likely to be the causes of the observed effects, as demonstrated by a two-step fractionation procedure of selected extracts. The toxic potential was more pronounced in fractions having polarity higher than those possessed by PAHs and PCBs. The suitability of the two in vitro test systems for assessing genotoxic and teratogenic effects of marine sediment extracts could be demonstrated.

Animals↗
PubMed2004

The discordance rate, a new concept for combining diagnostic decisions with analytical performance characteristics. 2. Defining analytical goals applied to the diagnosis of type 2 diabetes by blood glucose concentrations.

A novel statistical approach has recently been described to estimate diagnostic "errors" in method comparison studies. This procedure requires a population-based probability, pp, which describes the spread of values within the population under study, and an analytical probability, Pa, quantifying the risk of errors at a decision limit due to replacing one method by the other. The population probability was derived from 207 subjects who were submitted to an oral glucose tolerance test due to suspicion of type 2 diabetes. The new concept was then applied in a reverse mode by determining the analytical variability of glucose concentrations for a fixed discordance rate diagnosing type 2 diabetes. If a combined discordance rate (sum of positive and negative discordances) of 5% is allowed, a maximal imprecision of 3.7% can be tolerated in the absence of bias. In the presence of a 3.0% bias, the allowable imprecision must be reduced to 2.8%. The relationship between bias and imprecision followed a complex function and not a simple linear model. These allowable limits were achieved with venous plasma in the fasting state. The allowable analytical specifications were slightly more stringent with capillary blood. After a 2 h glucose challenge, higher error rates could be tolerated, indicating that post-load glucose concentrations have a higher diagnostic efficiency than fasting levels. The new concept has the advantage that it is derived from patient's samples in relation to diagnostic requirements.

Blood Glucose↗
PubMed2003

Are readily culturable bacteria in coastal North Sea waters suppressed by selective grazing mortality?

We studied the growth of six culturable bacterial lineages from coastal North Sea picoplankton in environmental samples under different incubation conditions. The grazing pressure of heterotrophic nanoflagellates (HNF) was reduced either by double prefiltration through 0.8- micro m-pore-size filters or by 10-fold dilutions with 0.2- micro m (pore-size) prefiltered seawater. We hypothesized that those gamma-proteobacterial genera that are rapidly enriched would also be most strongly affected by HNF regrowth. In the absence of HNF, the mean protein content per bacterial cell increased in both treatments compared to environmental samples, whereas the opposite trend was found in incubations of unaltered seawater. Significant responses to the experimental manipulations were observed in Alteromonas, Pseudoalteromonas, and Vibrio populations. No treatment-specific effects could be detected for members of the Roseobacter group, the Cytophaga latercula-C. marinoflava lineage, or the NOR5 clade. Statistical analysis confirmed a transient increase in the proportions of Alteromonas, Pseudoalteromonas, and Vibrio cells at reduced HNF densities only, followed by an overproportional decline during the phase of HNF regrowth. Cells from these genera were significantly larger than the community average in the dilution treatments, and changes in their relative abundances were negatively correlated with HNF densities. Our findings suggest that bacteria affiliated with frequently isolated genera such as Alteromonas, Pseudoalteromonas, and Vibrio might be rare in coastal North Sea picoplankton because their rapid growth response to changing environmental conditions is counterbalanced by a higher grazing mortality.

Alteromonas↗
PubMed2003

Discordance rate, a new concept for combining diagnostic decisions with analytical performance characteristics. 1. Application in method or sample system comparisons and in defining decision limits.

Method comparison studies are usually evaluated by several statistical tests (e.g., regression analysis) which sufficiently describe the analytical (dis)agreement between the results of two procedures. However, they do not provide any information how differences, if observed, influence diagnostic decision making. A novel statistical approach is described to test the clinical relevance of differences between two analytical procedures. The new procedure requires a population-based probability which describes the distribution of values within the population under study and an analytical probability quantifying the risk of errors due to replacing one method by the other. The population probability was derived from 171 subjects from two outpatient departments (internal medicine and dermatology) who were subjected to an oral glucose tolerance test because type 2 diabetes mellitus was suspected. The analytical probability was determined from duplicate glucose measurements in venous and capillary blood, and venous plasma in the fasting and 2 h post-challenge state by the routine method used in a central laboratory (Ebio analyzer) and a (POCT) glucometer (Elite). The two probabilities were combined into one "error rate" (discordance rate). The new concept was applied to three examples. In the first example, a comparison between two analytical systems led to discordance rates above 15%. After transforming the Elite analyzer results by a regression function, the discordance rate decreased below 5%, which was considered to be acceptable for the diagnostic purpose studied. In the second example, discordance rates were estimated by comparing different sample systems with each other. The use of whole blood in comparison with venous plasma led to discordance rates of 5-7% for venous blood and 7-10% for capillary blood. The same data set was also used in a third example to derive decision limits for capillary and venous blood from the established plasma values. The proposed procedure estimates the diagnostic error rate based on analytic performance characteristics and population probabilities. It extends the concept of (un)efficiency by including the effect of variability about a decision limit and the distribution of the measurement values in the patient population.

Blood Glucose↗
PubMed2003

Comparison of several point-of-care testing (POCT) glucometers with an established laboratory procedure for the diagnosis of type 2 diabetes using the discordance rate. A new statistical approach.

The applicability of point-of-care testing (POCT) glucometers for monitoring blood glucose concentrations has been demonstrated. However, their use in diagnosing type 2 diabetes is still debated. Therefore, a new statistical procedure for estimating discordance rates (DRs) was applied in comparing a well-established laboratory method (Ebio) with another laboratory method (Cobas Integra 700) and with several POCT glucometers (Accu-Chek, Accutrend, Elite, HemoCue, Omni) in detecting glucose intolerance states. All procedures led to parallel glucose concentration patterns in capillary blood, venous plasma, and venous blood during oral glucose tolerance tests. However, the mean concentrations differed more or less. The Ebio and Integra results agreed within a maximal deviation of 3%. In blood samples, the HemoCue and Accutrend results were closest to the laboratory procedures (Ebio and Integra) and the highest differences were obtained with the Elite. Comparing whole blood values with those obtained in the aqueous blood compartment (Omni), even greater differences were observed. When all procedures were referred to the same glucose standard, the Ebio, Integra, Accutrend, and Omni results remained almost unchanged, whereas the Elite "moved" toward the Ebio results, and the Accu-Chek results toward the Omni results. Thus, traceability to an aqueous standard was observed with the Ebio, Integra, Accutrend, and Elite in all three sample systems. The Accu-Chek was only traceable in the presence of albumin, and HemoCue was not traceable at all. The clinical relevance of the differences observed between Ebio and POCT glucometers was tested by comparing the relative number of discordant classifications. The highest DRs were observed in the fasting state. They were higher in capillary blood than in the other sample systems. The DRs were found higher with POCT glucometers than with the other established laboratory procedure (Integra). Thus, at least in the fasting state, all POCT glucometers were less reliable than the established laboratory procedures and above the chosen criteria of clinical acceptability (DR < or = 5%). After transforming all glucometer results with a regression function (bias correction), the DRs were less than 5% if compared with the Ebio procedure in all sample systems. In conclusion, the WHO recommendation not to use POCT glucometers for diagnosing type 2 diabetes must be supported. However, after proper recalibration, the tested systems were acceptable. Therefore, manufacturers should reconsider their calibration procedure. Those POCT procedures should be preferred that can be referred to aqueous glucose solutions.

Blood Glucose↗
PubMed2003

Detecting type 2 diabetes by a single post-challenge blood sample.

In the recent American Diabetes Association (ADA)/WHO recommendations, the oral glucose tolerance test (OGTT) was replaced by the measurement of a single fasting glucose concentration with a decision limit for the detection of type 2 diabetes mellitus (DM) reduced. This proposal, however, misses all cases of isolated post-prandial hyperglycaemia. Therefore, a study was undertaken to develop a post-challenge, one-sample mode of diagnosis. OGTT was performed in 240 high-risk subjects who were suspected to suffer from type 2 DM. Glucose concentrations were determined at 30 min intervals in the capillary blood, venous blood and plasma, and insulin was determined in venous plasma only. The test results were classified in non-disease and disease group according to the decision limits recommended by ADA/WHO. Furthermore, the early insulin response and an insulin sensitivity index were used to determine new cut-off values. These were identified as the concentrations demonstrating the highest diagnostic efficiency and were lower than the WHO limits. The 2 h post-load plasma concentration led to higher efficiency at a cut-off value of 9.0 mmol/l glucose (162 mg/dl) compared to concentrations of samples taken in the fasting state, at an earlier time of the OGTT, or in venous and capillary blood. Under this condition, 72 diabetic patients (35%) were detected in the study group (n = 207), whereas only 36 (17%) were found with one sample in the fasting state and 53 (26%) with two samples using the ADA/WHO criteria. Therefore, a single venous plasma sample taken after 2 h post-glucose challenge appeared to be most efficient for the early detection of DM.

Adult↗