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W Klein

Publications and source records attributed to W Klein.

At least 37 records · Page 2Linked to original sources
PubMed2003

Underlying issues including approaches and information needs in risk assessment.

Risk assessment requires a delicate consideration of the factors modifying exposure and effects. In this contribution a review is given of the qualitative and quantitative information needs that are essential for a proper risk assessment. The focus is on the details of metal exposure and exposure assessment, following the themes of environmental, physicochemical, and biological components that define exposure. Apart from a description of the principle processes and pathways, exposure assessment is placed in the context of risk assessment and its use in policy and regulatory decision making.

Animals↗
PubMed2003

Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE).

AIMS: There have been no large observational studies attempting to identify predictors of major bleeding in patients with acute coronary syndromes (ACS), particularly from a multinational perspective. The objective of our study was thus to develop a prediction rule for the identification of patients with ACS at higher risk of major bleeding. METHODS AND RESULTS: Data from 24045 patients from the Global Registry of Acute Coronary Events (GRACE) were analysed. Factors associated with major bleeding were identified using logistic regression analysis. Predictive models were developed for the overall patient population and for subgroups of patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina. The overall incidence of major bleeding was 3.9% (4.8% in patients with STEMI, 4.7% in patients with NSTEMI and 2.3% in patients with unstable angina). Advanced age, female sex, history of bleeding, and renal insufficiency were independently associated with a higher risk of bleeding (P<0.01). The association remained after adjustment for hospital therapies and performance of invasive procedures. After adjustment for a variety of potential confounders, major bleeding was significantly associated with an increased risk of hospital death (adjusted odds ratio 1.64, 95% confidence interval 1.18, 2.28). CONCLUSIONS: In routine clinical practice, major bleeding is a relatively frequent non-cardiac complication of contemporary therapy for ACS and it is associated with a poor hospital prognosis. Simple baseline demographic and clinical characteristics identify patients at increased risk of major bleeding.

Adult↗
PubMed2003

The role of low-molecular-weight heparins in cardiovascular medicine.

Low-molecular-weight heparins (LMWHs) have been shown to be as effective and safe as unfractionated heparin (UFH) for acute phase treatment of acute coronary syndrome in the absence of ST-elevation [unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI)]. LMWHs have practical advantages over UFH, including usual lack of requirement for laboratory monitoring of the anticoagulant response because of their favourable pharmacokinetic properties, and thus represent a simpler and more cost-effective option in clinical practice. The LMWH dalteparin has been shown to provide extended therapy benefit to high-risk UA/NSTEMI patients and can provide a protective bridge until revascularization. While revascularization procedures are now an established intervention for patients with UA/NSTEMI, a new approach for patients who cannot undergo immediate catheter intervention is to continue with medical treatment until revascularization is possible. LMWHs are currently being investigated for use in the catheterization laboratory, in patients undergoing percutaneous coronary intervention procedures, and in conjunction with thrombolytics for treatment of acute myocardial infarction.

Angina, Unstable↗
PubMed2003

Interaction of polymorphisms in the CARD15 and CD14 genes in patients with Crohn disease.

BACKGROUND: Associations of variations in the CARD15 gene (Arg702Trp, Gly908Arg and Leu1007fsinsC) and Crohn disease (CD) have been shown recently. These variations are neither necessary nor sufficient for the genetic predisposition of CD. Further genetic and environmental factors play a crucial role in the pathogenesis of CD. METHODS: To evaluate putative interactions between the CARD15 and CD14 genes in CD, a functionally relevant polymorphism in the promoter region (T/C at position -159) has been genotyped for 650 healthy controls and 253 patients with CD by RFLP analyses. CD patients were genotyped for the variations of the CARD15 gene. RESULTS: T allele and TT genotype frequencies of the CD14 promoter were significantly increased only in CD patients with at least one variation in the CARD15 gene compared to controls (P = 0.02 and 0.0002, respectively). No significant association was found in CD patients without any of the variations. CONCLUSION: Interactions of the CARD15 and CD14 genes, both of which are involved in the recognition of lipopolysaccharides, increase the risk for developing CD.

Carrier Proteins↗
PubMed2003

Validation of a field test for the non-invasive determination of badminton specific aerobic performance.

AIM: To develop a badminton specific test to determine on court aerobic and anaerobic performance. METHOD: The test was evaluated by using a lactate steady state test. Seventeen male competitive badminton players (mean (SD) age 26 (8) years, weight 74 (10) kg, height 179 (7) cm) performed an incremental field test on the badminton court to assess the heart rate turn point (HRTP) and the individual physical working capacity (PWC(i)) at 90% of measured maximal heart rate (HR(max)). All subjects performed a 20 minute steady state test at a workload just below the PWC(i). RESULTS: Significant correlations (p<0.05) for Pearson's product moment coefficient were found between the two methods for HR (r = 0.78) and velocity (r = 0.93). The HR at the PWC(i) (176 (5.5) beats/min) was significantly lower than the HRTP (179 (5.5) beats/min), but no significant difference was found for velocity (1.44 (0.3) m/s, 1.38 (0.4) m/s). The constant exercise test showed steady state conditions for both HR (175 (9) beats/min) and blood lactate concentration (3.1 (1.2) mmol/l). CONCLUSION: The data indicate that a valid determination of specific aerobic and anaerobic exercise performance for the sport of badminton is possible without HRTP determination.

Adolescent↗
PubMed2002

Precursory dynamics in threshold systems.

A precursory dynamics, motivated by the analysis of recent experiments on solid-on-solid friction, is introduced in a continuous cellular automaton that mimics the physics of earthquake source processes. The resulting system of equations for the interevent cycle can be decoupled and yields an analytical solution in the mean-field limit, exhibiting a smoothing effect of the dynamics on the stress field. Simulation results show the resulting departure from scaling at the large-event end of the frequency distribution, and support claims that the field leakage may parametrize the superposition of scaling and characteristic regimes observed in real earthquake faults.

Journal Article↗
PubMed2002

Aborted sudden death in a patient with a structurally normal heart: the Brugada syndrome.

We report a 37-year-old man with documented aborted sudden death. After resuscitation, the patient showed no structural heart disease but the ECG showed a right bundle-branch block with a descending ST segment elevation in leads V(1) and V(2). After transient normalization of the ECG, the administration of ajmaline led to spontaneous development of the distinct descending ST segment elevation in the right precordial leads and therefore to the diagnosis of Brugada syndrome. The incidence of sudden cardiac death among these patients is high. The only treatment is an implantable cardioverter-defibrillator (ICD). The Brugada syndrome should therefore be borne in mind in the differential diagnosis of sudden death.

Adult↗
PubMed2002

Self-organization in leaky threshold systems: the influence of near-mean field dynamics and its implications for earthquakes, neurobiology, and forecasting.

Threshold systems are known to be some of the most important nonlinear self-organizing systems in nature, including networks of earthquake faults, neural networks, superconductors and semiconductors, and the World Wide Web, as well as political, social, and ecological systems. All of these systems have dynamics that are strongly correlated in space and time, and all typically display a multiplicity of spatial and temporal scales. Here we discuss the physics of self-organization in earthquake threshold systems at two distinct scales: (i) The "microscopic" laboratory scale, in which consideration of results from simulations leads to dynamical equations that can be used to derive the results obtained from sliding friction experiments, and (ii) the "macroscopic" earthquake fault-system scale, in which the physics of strongly correlated earthquake fault systems can be understood by using time-dependent state vectors defined in a Hilbert space of eigenstates, similar in many respects to the mathematics of quantum mechanics. In all of these systems, long-range interactions induce the existence of locally ergodic dynamics. The existence of dissipative effects leads to the appearance of a "leaky threshold" dynamics, equivalent to a new scaling field that controls the size of nucleation events relative to the size of background fluctuations. At the macroscopic earthquake fault-system scale, these ideas show considerable promise as a means of forecasting future earthquake activity.

Animals↗
PubMed2002

Nucleation in systems with elastic forces.

Systems with long-range interactions when quenched into a metastable state near the pseudospinodal exhibit nucleation processes that differ from classical nucleation seen near the coexistence curve. In systems with long-range elastic forces the description of the nucleation process can be quite subtle due to the presence of bulk and surface elastic compatibility constraints. We analyze the nucleation process in a simple 2D model with elastic forces and show that the nucleation process generates critical droplets with a different structure than the stable phase. This has implications for nucleation in many crystal-crystal transitions, specifically martensites and shape memory alloys, and for the structure of the final state.

Journal Article↗
PubMed2002

Dilead mercury chromate(VI), Pb2HgCrO6.

The structure of Pb(2)HgCrO(6) (space group P-1) can be described as consisting of isolated [CrO(4)](2-) tetrahedra and nearly linear [HgO(2)](2-) dumb-bells, which form layers of composition [HgCrO(6)](4-). These are intercalated with corrugated pseudo-hexagonal Pb(2+) layers. The Pb(2+) cation is stereochemically active and has coordination 3+5.

Journal Article↗
PubMed2002

Movement of metolachlor and terbuthylazine in core and packed soil columns.

Movement of metolachlor and terbuthylazine including a bromide tracer was studied in core and packed soil columns in PVC pipes (80 mm diameter, 15 mm depth) with two German soil types viz: silt loam and loamy silt. The breakthrough curves (BTCs) for bromide indicated some preferential flow of water both under conventional tillage (CN) and no-till (NT) simulation with silt loam soil. The herbicides leached to a greater extent in NT columns than in CN columns. Leaching was higher in loamy silt soil than in silt loam soil under CN conditions. This result is in agreement with the higher sorption capacity of silt loam having higher organic carbon compared to loamy silt having low organic carbon. Adsorption strength of the herbicides did not affect their breakthrough time, but was reflected in the slope and maximum height of the BTCs. The BTCs showed the expected inverse relationship between leaching and adsorption with greater mobility of the weakly-sorbed metolachlor than the more strongly sorbed terbuthylazine. Maximum amounts of the applied herbicides were recovered from the top soil layer in intact columns. Metolachlor was more mobile in packed columns than in core columns.

Acetamides↗
PubMed2002

Inhibitors in the NFkappaB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations.

Multiple sclerosis (MS) is an autoimmune disease displaying different clinical courses. In this multifactorial disease complex environmental as well as genetic predisposition factors contribute to the disease manifestation. Following the candidate gene approach we analysed several genes of the NFkappaB cascade, which are prime candidates for MS because of their involvement in almost all immunological reactions. MS association was excluded for the NFKB1 and NFKB3 genes, which show remarkably low degrees of polymorphism. The genes of NFkappaB inhibitors exhibit more sequence variations. In the IKBL gene a predisposing allele was identified (13.1% vs 7.5% in the control group, P < 0.001). This difference in the allelic distribution was even increased in the group of MS patients with a relapsing remitting course of the disease (14.9%, P < 0.0001). A protecting allele was found in the NFKBIA promotor for the patients with primary progressive MS (15.4% vs 28.4% in the control group, P < 0.01). Given predisposing alleles increase MS risk dramatically in certain combinations.

Adaptor Proteins, Signal Transducing↗
PubMed2002

A polymorphism in the IL11 gene is associated with ulcerative colitis.

Inflammatory bowel diseases (IBD) are multifactorial disorders characterised by the host's inability to limit the inflammatory response to luminal antigens. The association of polymorphisms in the CARD15 gene with Crohn's disease (CD) demonstrates the relevance of activated transcription factor NF(kappa)B in mononuclear cells. Interleukin 11 (IL11) mediates anti-inflammatory effects and is able to downregulate LPS-induced NF(kappa)B activation. The IL11 gene is therefore a good candidate involved in genetic predisposition to IBD. To evaluate the role of the IL11 gene in IBD, two polymorphisms, including a dinucleotide repeat in the promoter region, have been genotyped in 222 patients with CD, 152 patients with ulcerative colitis (UC) and 400 healthy controls. PCR-SSCP analysis of the coding region revealed a single polymorphism in exon 4 leading to an amino acid exchange (G335A; R112H), not significantly associated with either disease. Dinucleotide repeat frequencies of the IL11.A1 allele and of IL11.A1 homozygous individuals were significantly increased among the patients with UC (P < 0.002 and (P < 0.003, respectively) but not with CD. Altered expression of IL11 appears to be involved in the genetic predisposition of UC.

Alleles↗
PubMed2002

[Efficiency and safety of ACE-inhibiting imidapril in patients with essential hypertension].

In a survey including 2224 patients with essential hypertension we investigated efficacy and tolerability of the new ACE-inhibitor Imidapril. Mean blood pressure at baseline was 172 +/- 19/98 +/- 10 mmHg. Treatment with Imidapril 5-20 mg once daily caused a decrease in BP by 21 +/- 17/11 +/- 10 mmHg (p < 0.01/0.01). Systolic BP was reduced by > 15 mmHg in 71% diastolic BP by > 10 mmHg in 64% of patients. 29% of patients achieved the treatment goal of a blood pressure < or = 140/90 within an average of 26 days. Imidapril decreased pulse-pressure (one of the most important risk markers in hypertension) by 18% (74 +/- 17 to 61 +/- 11 mmHg, p < 0.01). ACE-inhibitor related adverse effects (cough, vertigo, headache, pruritus, tachycardia, orthostatic dysregulation or nausea) were observed in 38 patients (< 2%). Efficacy of treatment was graded by the physician in charge of the patient care by means of a questionnaire. Gradings were excellent or good in 96% of patients, moderate in 3% and poor in < 1%. In summary, the effects of Imidapril on blood pressure were comparable to those of other ACE-inhibitors. However, the frequency of adverse effects was low and similar to that of angiotensin-II-antagonists.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Management of acute coronary syndromes. Variations in practice and outcome; findings from the Global Registry of Acute Coronary Events (GRACE).

AIMS: Despite advances in the treatment of acute coronary syndromes based on randomized trial data and published guidelines, the extent to which such treatments are applied in practice remains uncertain. Data from clinical trials derive from selected geographical areas and in highly selected populations of patients, and hence may not reflect the overall population. The aim of the study was to investigate variations in hospital management and outcome using unselected data collected in the prospective Global Registry of Acute Coronary Events (GRACE). METHODS AND RESULTS: The 95 hospitals in GRACE were organized into 18 population-based clusters in 14 countries. Information was recorded about patient management and outcome during hospitalization and after discharge. Data on treatments administered were analysed by baseline condition, hospital type, by the presence or absence of a catheterization laboratory, and by geographical region. Of 11543 patients, 44% had an admission diagnosis of unstable angina, 36% presented with myocardial infarction, 9% were admitted to rule out a myocardial infarction, 7% had chest pain and 4% were hospitalized for 'other cardiac' and 'non-cardiac' diagnoses. Of the total GRACE population 38% had a final diagnosis of unstable angina, 30% ST-segment elevation myocardial infarction, 25% non-ST-segment elevation myocardial infarction, and 7% of 'other cardiac' and 'non-cardiac' final diagnoses. The event rates for hospital death or reinfarction were six and 2% for non-ST-segment elevation myocardial infarction, seven and 3% for ST-segment elevation myocardial infarction, and 3% hospital death for unstable angina. The use of aspirin was similar across all hospital types and geographical regions. In contrast, the use of percutaneous coronary intervention and glycoprotein IIb/IIIa inhibitors was higher (P<0.0001) in teaching hospitals and hospitals with catheterization laboratories and was also higher in the United States. At discharge a higher percentage (P<0.0001) of patients received angiotensin-converting enzyme inhibitors in hospitals without catheterization laboratories. The use of statins was lower in non-teaching hospitals and in centres without a catheterization laboratory. CONCLUSIONS: The GRACE study reveals substantial differences in the management of patients based on hospital type and geographical location. Further analyses will determine whether such variations translate into differences in longer term outcomes. GRACE provides a multinational reference for the implementation of therapies of proven efficacy.

Acute Disease↗
PubMed2002

Coronary anatomy predicts presence or absence of renal artery stenosis. A prospective study in patients undergoing cardiac catheterization for suspected coronary artery disease.

AIMS: This study aimed to determine the prevalence of renal artery stenosis (RAS) and associated risk factors in patients undergoing cardiac catheterization for suspected coronary artery disease (CAD). METHODS: One hundred and seventy-seven consecutive patients (62 females) with a serum creatinine concentration <2.0mg.dl(-1) were studied. Abdominal aortography followed cardiac catheterization to screen for RAS. RESULTS: In 110 patients (62%) CAD and in 19 patients (11%) significant RAS (luminal narrowing of >or=50%) were detected, 12 of whom had high grade (>or=70%) RAS, and two subjects had significant RAS without CAD. Patients with RAS were older (67+/-8 vs 61+/-11 years, mean+/-SD;P =0.004), had higher systolic blood pressure (150+/-15 vs 138+/-20 mmHg;P =0.005), a lower glomerular filtration rate (GFR; 61+/-16 vs 80+/-22 ml.min(-1), P<0.001) and more often diabetes mellitus (69% vs 30%; P=0.004). In multivariate analysis a low GFR and the extent of CAD were independent predictors of RAS. The presence of >2 significant coronary lesions predicted RAS (sensitivity 0.84, specificity 0.77, positive predictive value 0.30, negative predictive value 0.98). CONCLUSION: Screening for RAS in patients with >2 diseased coronary segments has a high diagnostic yield, which is even greater in the presence of a reduced GFR, diabetes mellitus, and elevated systolic blood pressure.

Aged↗