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Biomedical subjects

W Klein

Publications and source records attributed to W Klein.

At least 37 records · Page 2Linked to original sources
PubMed2002

Human paraoxonase 1 gene polymorphisms and the risk of coronary heart disease: a community-based study.

Published data on the association between paraoxonase1 (PON1) polymorphisms and coronary heart disease (CHD) have yielded controversial results. The objective of this study was to determine the possible relationship between the two human PON1 amino acid variants, the Leu55Met and the Gln192Arg polymorphism, and the risk of CHD in a community-dwelling cohort of European ancestry. PON1 genotypes of 152 women and 151 men out of 1,998 randomly selected individuals aged 44-75 years were determined by polymerase chain reaction-based restriction enzyme digestion. Study participants underwent cardiological examination including a structured clinical interview, resting ECG, exercise testing and echocardiography. The diagnosis of CHD was based on history and/or appropriate findings during cardiac examination. Evidence for CHD was found in 43 (14.2%) study participants. The Leu/Leu (LL), Leu/Met (LM) and Met/Met (MM) genotypes at position 55 were noted in 131 (43.2%), 128 (42.2%) and 44 (14.5%) subjects; the Gln/Gln (QQ), Gln/Arg (QR) and Arg/Arg (RR) genotypes at codon 192 occurred in 167 (55.1%), 118 (38.9%) and 18 (5.9%) individuals, respectively. Homozygosity for the 55L-allele was significantly associated with CHD (p = 0.02), while the Gln192Arg polymorphism had no effect (p = 0.16). Logistic regression analysis demonstrated age (odds ratio 1.06/year), smoking (odds ratio 2.86), HDL cholesterol (odds ratio 0.94/mg/dl) and the paraoxonase LL genotype (odds ratio 2.25) to be significant predictors of CHD. These data suggest that the paraoxonase LL genotype at position 55 may present a risk factor for CHD.

Adult↗
PubMed2001

Instability of Alexander-McTague crystals and its implication for nucleation.

We show that the argument of Alexander and McTague, that the bcc crystalline structure is favored in those crystallization processes where the first-order character is not too pronounced, is not correct. We find that any solution that satisfies the Alexander-McTague condition is not stable. We investigate the implication of this result for nucleation near the pseudospinodal in near-meanfield systems.

Journal Article↗
PubMed2001

Transformation of dissolved organic matter (DOM) and 14C-labelled organic contaminants during composting of municipal biowaste.

Composting of municipal biowaste in the presence of 14C-labelled organic contaminants was studied in an attempt to characterize the mobilization potential of dissolved organic matter (DOM) for hydrophobic contaminants. The properties and transformation of DOM extracted from municipal biowaste compost with 10 mM KCl at six stages during 370 days of composting were investigated. DOM was fractionated into molecular weight fractions by ultrafiltration, and DOM structure was studied using CPMAS 13C-NMR- and UV-spectroscopy. The distribution of 14C-labelled model substances (DEHP, pyrene, simazine) upon molecular weight fractions was investigated by ultrafiltration, and association to DOM was studied performing flocculation experiments. The binding capacity of DOM for the model substances was of secondary influence for the mobilization because the intense biochemical reactions during composting pre-dominated the fate of the substances. Composting favoured the degradation of model substances to polar metabolites and supported their binding to the DOM matrix. DEHP and simazine were mainly found in the low- to medium-molecular DOM fraction and showed a small amount of DOM-associated radioactivity (approx. 10%). Pyrene and its metabolites had high affinities to high-molecular DOM. However, a direct relationship between DOM-quality and enhancement of pyrene solubility was not visible. After 120 days of composting DOM showed the highest binding capacity for hydrophobic contaminants.

Biodegradation, Environmental↗
PubMed2001

Diagnosis and risk stratification in patients with acute coronary syndromes according to ESC guidelines.

Diagnosis and risk stratification of patients with acute coronary syndromes remain extremely important in order to avoid unnecessary hospitalizations on the one hand, and to improve prognosis of these patients on the other. For diagnosis of acute coronary syndromes, an ECG should be obtained at rest, troponin T and I should be measured on admission and again 6 to 12 h later, and myoglobin or CK-MB should be determined in patients with recent syndromes and those with recurring ischemia. Risk should be assessed upon admission and repeatedly during the hospital stay. Early risk indicators are: age, male sex, previous manifestation of coronary artery disease, history of left ventricular dysfunction or congestive heart failure and ongoing chest pain, as well as ST depression, transient ST segment elevation, and elevated levels of troponin T or I. Longer term risk assessment in unstable coronary artery disease includes rest and stress echocardiography, exercise ECG, thallium scintigraphy, as well as coronary angiography and left ventriculography. Markers of high long-term risk are old age, prior history of myocardial infarction, diabetes, elevated levels of C-reactive protein, and the extent of coronary artery disease and left ventricular dysfunction.

Acute Disease↗
PubMed2001

Nonlinear network dynamics on earthquake fault systems.

Earthquake faults occur in interacting networks having emergent space-time modes of behavior not displayed by isolated faults. Using simulations of the major faults in southern California, we find that the physics depends on the elastic interactions among the faults defined by network topology, as well as on the nonlinear physics of stress dissipation arising from friction on the faults. Our results have broad applications to other leaky threshold systems such as integrate-and-fire neural networks.

Journal Article↗
PubMed2001

Stereoselective effects of (R)- and (S)-carvedilol in humans.

Carvedilol is currently used as the racemic mixture, (R,S)-carvedilol, consisting of equal amounts of (R)-carvedilol, an alpha-blocker, and (S)-carvedilol, an alpha- and beta-blocker, which have never been tested in their optically pure forms in human subjects. We performed a randomized, double-blind, placebo-controlled, crossover study in 12 healthy male volunteers. Subjects received single oral doses of 25 mg (R,S)-carvedilol, 12.5 mg (R)-carvedilol, 12.5 mg (S)-carvedilol, and placebo at 8 AM as well as at 8 PM. Exercise was performed at 11 AM, and heart rate and blood pressure were measured at rest and after 10 min of exercise. Urine was collected between 10 AM and 6 PM, as well as between 10 PM and 6 AM, and the amounts of urinary 6-hydroxy-melatonin sulfate (aMT6s) were determined by RIA. Compared to placebo, (R)-carvedilol increased heart rate during exercise (+4%, P < 0.05) and recovery (+10%, P < 0.05); (S)-carvedilol decreased heart rate during exercise (-14%, P < 0.05) and recovery (-6%, P < 0.05), and systolic blood pressure during exercise (-12%, P < 0.05); (R,S)-carvedilol decreased heart rate during exercise (-11%, P < 0.05), and systolic blood pressure at rest (-7%, P < 0.05) and during exercise (-10%, P < 0.05). None of the agents had any significant effect on the release of aMT6s. Our results indicate that only (S)-carvedilol causes beta-blockade, whereas (R)-carvedilol appears to increase sympathetic tone, presumably as a physiological reaction to the decrease of blood pressure caused by alpha-blockade. None of the drugs had any influence on melatonin release. The weak clinical net effect of beta-blockade of (R,S)-carvedilol at rest might be one reason why this drug causes fewer side effects than other beta-blockers, such as a reduction of nocturnal melatonin release.

Administration, Oral↗
PubMed2001

Eccentric head positions bias random generation of leftward and rightward handle-bar rotations.

We explored the effects of eccentric head positions on rapid rotations of a handle-bar in a modified randomization task. Subjects had to generate a random sequence of leftward and rightward handle-bar rotations; each pre-selected rotation was produced in response to a visual signal as rapidly as possible. Eccentric head positions induced a bias in that handle-bar rotations in the direction of the eccentric head position were chosen more frequently than handle-bar rotations in the opposite direction. This is consistent with previous evidence on a spatial coupling. In contrast to response selection, response initiation was not affected by eccentric head positions. The kinematic characteristics, however, differed: rotations in the direction of the eccentric head position were of larger amplitude and longer duration than rotations in the opposite direction. This difference may have been secondary to a difference in the start positions of the handle-bar, which were shifted in the direction opposite to the eccentric head position.

Adult↗
PubMed2001

Differing beta-blocking effects of carvedilol and metoprolol.

BACKGROUND: Metoprolol is a beta(1)-selective beta-adrenergic antagonist while carvedilol is a non-selective beta-blocker with additional blockades of alpha(1)-adrenoceptors. Administration of metoprolol has been shown to cause up-regulation of beta-adrenoceptor density and to decrease nocturnal melatonin release, whereas carvedilol lacks these typical effects of beta-blocking drugs. AIMS: To compare beta-blocking effects of metoprolol and carvedilol when applied orally in healthy subjects. METHODS: We investigated the effects of single oral doses of clinically recommended amounts of metoprolol (50, 100 and 200 mg) and carvedilol (25, 50 and 100 mg) to those of a placebo in a randomised, double-blind, cross-over study in 12 healthy male volunteers. Two hours after oral administration of the drugs heart rate and blood pressure were measured at rest, after 10 min of exercise, and after 15 min of recovery. RESULTS: Metoprolol tended to decrease heart rate during exercise (-21%, -25% and -24%) to a greater extent than carvedilol (-16%, -16% and -18%). At rest, increasing doses of metoprolol caused decreasing heart rates (62, 60 and 58 beats/min) whereas increasing doses of carvedilol caused increasing heart rates (62, 66 and 69 beats/min), 50 and 100 mg carvedilol failed to differ significantly from the placebo (71 beats/min). CONCLUSIONS: We conclude that clinically recommended doses of carvedilol cause a clinically relevant beta-blockade in humans predominantly during exercise where it appears to be slightly (although not significantly) less effective than metoprolol. On the other hand, the effects of carvedilol on heart rate at rest appear rather weak, particularly in subjects with a low sympathetic tone. This might be caused by a reflex increase on sympathetic drive secondary to peripheral vasodilation resulting from the alpha-blocking effects of the drug. These results might be helpful in explaining why carvedilol, in contrast to metoprolol, may fail to cause up-regulation of beta-adrenoceptor density and does not decrease nocturnal melatonin release. This, in turn, may be a reason for the weak side-effects of carvedilol resulting from the beta-blockade. In addition, our data might be of interest in the interpretation of the forthcoming results of the COMET trial, although it has to be emphasised that they were derived from healthy subjects and, therefore, cannot be directly extrapolated to patients with heart failure.

Administration, Oral↗
PubMed2001

The CARE-HF study (CArdiac REsynchronisation in Heart Failure study): rationale, design and end-points.

BACKGROUND: Cardiac resynchronisation is a promising new intervention for patients with heart failure, left ventricular systolic dysfunction and ventricular dyssynchrony. OBJECTIVE: The CARE-HF trial is designed to evaluate the long-term effects of cardiac (atrio-bi-ventricular) resynchronisation on the mortality and morbidity of patients with heart failure due to left ventricular systolic dysfunction already receiving diuretics and optimal medical therapy with ACE inhibitors and beta-blockers (where indicated and tolerated). METHODS AND RESULTS: Approximately 800 patients will be randomised to device therapy or control and followed for a minimum of 18 months. A pragmatic study design has been chosen that does not attempt to conceal allocation from investigators or patients because it is impossible to guarantee maintenance of blinding for the duration of the study. The end-points committee will adjudicate events in a blinded fashion. Since cardiac resynchronisation may alter other aspects of the management of the patient, as would occur in clinical practice, the study should be considered a comparison of strategies rather than simply of a device. The primary end-point is all-cause mortality or unplanned cardiovascular hospitalisation. The study should complete recruitment during 2002 and report in 2004.

Adrenergic beta-Antagonists↗
PubMed2001

Interleukin-4 and interleukin-4 receptor gene polymorphisms in inflammatory bowel diseases.

Imbalances in the regulation of Th1 and Th2 lymphocytes are crucial in inflammatory bowel diseases. Interleukin-4 is secreted by Th2 lymphocytes and downregulates cytokine production from Th1 lymphocytes. Functionally relevant polymorphisms have been described in the interleukin-4 and the interleukin-4 receptor alpha genes. Association of inflammatory bowel diseases with these polymorphisms has been reported recently suggesting high transcription and enhanced signalling activity in Crohn's disease. Our study, comprising 211 patients with Crohn's disease, 147 patients with ulcerative colitis and 446 healthy controls revealed significant association of Crohn's disease with the -590 T allele of the interleukin-4 gene (P = 0.03). This allele entails reduced expression of IL-4. The reason for these contrasting findings may be discussed in the context of a putatively predisposing allele in linkage disequilibrium with the alleles of the interleukin-4 gene.

Alleles↗
PubMed2001

[Increased demand for psychosomatic consultation service (C-service) in a department of cardiology/pneumology due to psychometric screening].

The aim of the study was to test whether the routine use of the Hospital Anxiety and Depression Scale HADS changes the frequency and the duration of calling the psychosomatic C-service. 70% of all patients of the department of cardiology/pneumology were registered by the HADS. Psychometric screening raised the number of patients checked by the C-service (15.3 vs. 2.7% of all patients of the department; p < 0.01) and reduced the duration of the call for the C-service (2.7 vs. 6.4 days; p < 0.01) compared to conventional C-service. Elevated scores in HADS were found in 26% of the patients (21% depression, 12% anxiety).

Aged↗
PubMed2001

Sorption behavior of metolachlor, isoproturon, and terbuthylazine in soils.

The sorption-desorption of metolachlor [2-chloro-N-(ethyl-6-methyl phenyl)-N-(2-methoxy-1-methyl ethyl) acetamide], isoproturon [3-(4-isopropyl phenyl)-1,1-dimethyl urea] and terbuthylazine [N6-tert butyl-6-chloro-N4-ethyl-1,3,5-triazine-2,4-diamine] herbicides was studied in two German soils at 1:10 soil to water ratio by batch method. Equilibrium of herbicides between soil and water (0.01 M CaCl2) was attained in 2 h. Sorption data fitted very well to Freundlich equation, represented by very high correlation coefficient (r2 > 0.934). Comparison of Freundlich K values indicated that sorption of all the three herbicides was most pronounced in soil having higher organic carbon content. Koc values were as expected nearly identical for each herbicide in the two soils. The Freundlich constant (1/n) was about 1 for metolachlor and less than 1 for terbuthylazine and isoproturon indicating a L-type of sorption isotherms. Desorption of all the three herbicides showed hysteresis. Nearly equal amounts of metolachlor, isoproturon and terbuthylazine were desorbed from both soils. There was a good correlation between Koc and solubility.

Acetamides↗
PubMed2001

The polymorphism at position -174 of the IL-6 gene is not associated with inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel diseases (IBD) are multifactorial disorders, characterized by failure to limit the inflammatory response to luminal antigens. Genetic factors play an important role in the pathogenesis, but little is known about the accountable genes. Increased secretion of pro-inflammatory cytokines appears crucial in the initiation of the inflammatory response. METHODS: To evaluate the role of the IL-6 gene in IBD, a functionally relevant polymorphism in the promoter region (G/C at position -174) has been genotyped in 169 patients with Crohn's disease (CD), 133 patients with ulcerative colitis (UC) and 440 healthy controls by using restriction fragment length polymorphism (RFLP) analysis. RESULTS: No significant differences were apparent in the allele, genotype and carrier frequencies between patients and controls. CONCLUSION: High secretion of IL-6 does not seem to play a major role in the genetic predisposition to IBD.

Alleles↗
PubMed2001

Role of the Bacillus subtilis fatty acid desaturase in membrane adaptation during cold shock.

In our attempt to understand the cold shock response of Bacillus subtilis, we report on the role of the B. subtilis fatty acid desaturase (FA-D) Des during membrane adaptation to low temperatures and demonstrate its importance during cold shock. A des null mutant was constructed and analysed in comparison with its parental strain. Growth studies and large-scale comparative fatty acid (FA) analysis revealed a severe cold-sensitive phenotype of the des deletion mutant during the absence of isoleucine and showed that four unsaturated fatty acid (UFA) species differing in length, branching pattern and position of the double bond are synthesized in B. subtilis JH642 but not in the des null mutant. Apart from the lack of UFA synthesis, the FA-D deletion strain showed a dramatically altered saturated fatty acid (SFA) profile at the onset of the stationary growth phase in the presence of exogenous isoleucine sources. Expression of des integrated in trans at the amyE locus of the des deletion strain not only cured the cold-sensitive phenotype observed for the des mutant but allowed much better growth than in strain JH642 after a shift from 37 degrees C to 15 degrees C. These results show that, during cold shock adaptation, des expression can completely replace the isoleucine-dependent, long-term, FA branching adaptation mechanism. We conclude that the crucial aspect in cold adaptation of the cytoplasmic membrane is not its specific molecular composition but rather its physical status in terms of its fluidity.

Adaptation, Physiological↗
PubMed2001

[Angiotensin I receptor blockers for heart failure].

Angiotensin conversion enzyme inhibitors (ACE-inhibitors) have long been the only possibility to influence the renin angiotensin system (RAS) and its often fatal influences in heart failure. In the last few years specific blockers of the angiotensin 1 receptor (AT I blockers) offered a new possibility for this therapeutic target. In contrast to ACE inhibitors AT I blockers are relatively new and, therefore, few data on heart failure are available. The first head-to-head studies that compared AT I blockers and ACE-inhibitors and their effect on mortality did not show a reduced mortality in the AT I blocker groups. Based on the available data AT I blockers should be used in heart failure patients who are intolerant of ACE-inhibitors.

Angiotensin Receptor Antagonists↗