Biomedical subjects
E Ernst
Publications and source records attributed to E Ernst.
[Ergonomic aspects of sitting].
Although basing on anecdotal rather than scientific evidence, it is now thought that adopting a poor posture while seated is involved in the present "epidemic" of back pain. This poses the question as to what constitutes a correct sitting posture. Surprisingly, the literature offers little verifiable information. An adjustable angle between the seat and the backrest would appear favorable. Armrests are also recommended for certain activities. It is important that the chair can be adapted to the dimensions of the individual, and to the needs dictated by the surroundings. Innovative chair designs are controversial, and most may be recommended only as a "training device". Car seats create special demands, and should always be subjected to functional testing. In conclusion, scientific data on the ergonomics of sitting are sparse. Further controlled studies are urgently needed.
Cytotoxic effects of hexavalent chromium in cultured murine macrophages.
The in vitro effect of hexavalent chromium (CrVI) on mouse peritoneal macrophages was investigated. Our results demonstrate the existence of a threshold concentration of 2.5 microM of CrVI above which chromium affects the viability of macrophages in a concentration dependent manner. Morphological changes were seen with increasing concentrations of chromium. Evidence is presented that protein production (virus-induced interferon) in murine peritoneal macrophages was impaired by hexavalent chromium at low concentrations, while random migration and phagocytic activity were only affected at high concentrations of CrVI.
Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids.
The effects of dietary supplementation with n-3 fatty acids on the level of cytokines and complement activation in plasma from patients with rheumatoid arthritis were examined. Thirty-two patients with active rheumatoid arthritis were included in a 12-week double-blind, randomized study of dietary supplementation with n-3 fatty acids (3.6 g per day) or placebo. The cytokines were measured in plasma before and after treatment with fish oil or placebo. In general, cytokine values at the upper limits of the calculated normal areas were found. The Interleukin-1 beta concentration in plasma was reduced significantly after 12 weeks of dietary supplementation with fish oil (p < 0.03). No significant difference was observed in the placebo group. The tumour necrosis factor alpha activity in plasma did not change significantly (p = 0.167). No significant changes were observed in the degree of complement activation. The clinical status of the patients was improved in the fish oil group, but not in the placebo group, judged by Ritchie's articular index (p < 0.02). We conclude that dietary supplementation with n-3 fatty acids results in significantly reduced plasma IL-1 beta levels in patients with rheumatoid arthritis. Even though the cytokine levels were low, the anti-inflammatory effect of n-3 fatty acids could in part be explained by their ability to decrease cytokine production.
Oral contraceptives, fibrinogen and cardiovascular risk.
Today there can be little doubt about the fact that fibrinogen is a major, independent cardiovascular risk factor. Therefore one should consider circumstances that might lead to an increment of plasma fibrinogen levels. Oral contraceptives (OCs) have been reported to be associated with high fibrinogen. The present review details the information on this potentially important side effect. Cross sectional studies report both increased fibrinogen in OC users as well as no such change. Longitudinal studies yield a much clearer picture. They demonstrate that OCs lead to a significant rise in fibrinogen within 1-3 months of medication. The effect seems to be strongest in OCs with a high oestrogen concentration. Upon discontinuation, fibrinogen returns to normal, usually within about 3 months. These findings suggest that OC use might contribute to the cardiovascular risk partly by elevating fibrinogen levels.
The possible role of hemorheology in atherothrombogenesis.
Conventional risk factors predict only about 30-50% of incidental cases in cardiovascular diseases, which are still the leading cause of death in western societies. During the last decade, the importance of thrombosis as an essential mechanism in acute myocardial infarction (AMI) and stroke has been established. The introduction of thrombolysis has led to an impressive reduction in AMI case fatality and possibly also to a substantial amelioration of its prognosis. Evidence from experimental, clinical and epidemiological studies suggest, that several hemostatic and hemorheological factors (e.g., fibrinogen, Factor VII, plasma viscosity, hematocrit, red blood cell aggregation, total white cell count) might not only play an important role in the evolution of acute thrombotic events, but may also take part in the pathophysiology of atherosclerosis. An increasing number of studies reports altered hemostatic and hemorheological parameters to be associated with smoking, hyperlipoproteinemia, and high blood pressure, as well as with adverse dietary habits and other life-style factors. To date, their way of interaction with the atherosclerotic process is poorly understood. Hemorheological or hemostatic mechanisms that might promote thromboatherogenesis include the predisposition to thrombosis via a hypercoagulable state, the enhancement of atherosclerosis by fibrinogen and its metabolites, and finally the reduction of blood flow through various rheological effects (e.g., increase in plasma viscosity and red cell aggregation, or leukocyte activation). Future research should focus in more detail on the interrelationship between accepted risk factors and the hemostatic system as well as hemorheological parameters. Deeper insight into the mechanisms involved might lead to new preventive strategies as well as to therapeutic procedures in the management of atherosclerosis and associated thrombotic events.
Production of stable anti-digoxin Fv in Escherichia coli.
We have created a bacterial expression-export system and have used it to express (14 mg l-1) the variable region fragment (Fv) of an anti-digoxin antibody (26-10) in Escherichia coli. The expression-export plasmid contains a T7 promoter and the E. coli signal sequences ompA [Movva et al., J. biol. Chem. 255, 27-29 (1980)] and phoA [Inouye et al., J. Bacteriol. 149, 434-439 (1982)] fused to heavy chain (VH) and light chain (VL) variable region sequences to generate an artificial cistron. The 26-10 Fv protein made using this system was soluble, unlike many other expression systems which produce insoluble proteins in the form of inclusion bodies. The 26-10 VH and VL proteins were cleaved at their mature N-termini and exported into the bacterial periplasm where they could be easily extracted and affinity purified on ouabain-Sepharose. 26-10 Fv bound to digoxin with similar affinity and specificity as the whole 26-10 antibody (Ka for Fv, 1.3 x 10(9) M-1, Ka for IgG, 7 x 10(9) M-1). 26-10 Fv appears to be remarkably stable in comparison with other Fv fragments. The half-life for chain dissociation of 26-10 Fv was 48 hr compared to the reported 1.5 hr half-life of McPC603 Fv. We present the proton NMR spectra of the 26-10 Fv as preliminary evidence that this expression-export system can be used to facilitate the analysis of the solution structure of 26-10 Fv by NMR.
Fibrinogen: the plot thickens.
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The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial.
STUDY OBJECTIVE: To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with rheumatoid arthritis. DESIGN: Multicenter, randomized, placebo controlled, double blind. SETTING: Three Danish hospital Departments of Rheumatology. PATIENTS: Fifty-one patients with active rheumatoid arthritis. INTERVENTION: Random allocation to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with fat composition as the average Danish diet. MAIN RESULTS: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. CONCLUSIONS: Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis.
Plasma concentration levels of apolipoprotein A-I, apolipoprotein B and lipoprotein (a) in Greenland Inuit (Eskimos).
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Experimentally induced lipid peroxidation after exposure to chromium, mercury or silver: interactions with carbon tetrachloride.
Chromium, along with other heavy metals, induces an increased production of malondialdehyde (MDA), an indicator of lipid peroxidation, in liver and kidney tissue of NMRI male mice. After acute intoxications MDA levels remain high for 60 min. and thereafter return to normal in the kidney whereas MDA levels in liver are still increased 48 hr after exposure. Exposure of mice to chromium, mercury, or silver and another stimulator of lipid peroxidation, carbon tetrachloride, showed synergism between inorganic mercury and CCl4. Pre-exposure to chromium, organic mercury, or silver at selected doses did not enhance CCl4-toxicity as measured by organ content of MDA.
A viscometric method of measuring plasma fibrinogen concentrations.
A technique based on deducing the viscosity of serum from that of plasma was compared with the commonly used Clauss method. The two methods correlated closely (r = 0.914). The reproducibility of the viscometric method was slightly poorer than the Clauss technique at low fibrinogen concentrations, equal to that at medium fibrinogen concentrations, and marginally better at high concentrations. Fibrinogen can therefore be measured reasonably accurately with the viscometric method, and can be recommended as an alternative for laboratories possessing a viscometer.
Association between rheology and components of lipoproteins in human blood. Results from the MONICA project.
BACKGROUND: Recent studies have suggested that several hemostatic factors, leukocyte count, and plasma viscosity are predictive of coronary heart disease. Detailed analyses on lifestyle correlates, in particular plasma lipids and lipoproteins, of determinants of blood rheology have not been reported from epidemiological studies. METHODS AND RESULTS: We studied the relation between determinants of blood rheology and components of lipoproteins in a large sample of a population aged 25-64 years. The rheological parameters investigated were plasma viscosity, hemoglobin, and total serum protein; the lipoprotein variables included total cholesterol, high density lipoprotein (HDL) cholesterol, and the apoproteins A-I, A-II, and B. Covariables considered for possible confounding effects were age, body mass index, smoking behavior, alcohol consumption, and hypertension. Plasma viscosity was found to have a positive linear association with total cholesterol and apoprotein B (partial correlations after adjustment for all covariables including total serum protein for men and women were r = 0.23/0.19 and 0.24/0.25, respectively) and a small negative linear association with HDL cholesterol (r = -0.14/-0.10) and with apoprotein A-I (r = -0.08/-0.06). Polynomial regression showed a strong quadratic relation with HDL cholesterol in men, whereas no other variable revealed an appreciable deviation from linearity. The covariables had only a small, if any, confounding effect. Total serum protein, after control for the covariables, appeared to be associated only with total cholesterol. No association was found with hemoglobin. CONCLUSIONS: We conclude that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. However, the finding that in particular men with very low HDL cholesterol exhibit increased plasma viscosity cannot be explained in pure rheological terms but may be, at least in part, the result of concomitant hypertriglyceridemia. This was not assessed in this study.
Plasma viscosity as a cardiovascular risk factor.
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Does pentoxifylline prolong the walking distance in exercised claudicants? A placebo-controlled double-blind trial.
The aim of this study was to test whether in claudicants oral pentoxifylline, given for twelve weeks in addition to physical exercise, prolongs the walking distance more than placebo plus exercise. Forty outpatients were randomized into group A (2 x 600 mg oral pentoxifylline per day) or group B (placebo). Both groups received the same exercise program in addition. The maximal and painfree walking distances and blood viscosity were measured. Intergroup differences in terms of blood viscosity reached the level of significance only after twelve weeks (p = 0.006 at shear rate of 94.5 s-1), but values of group A continuously decreased and those of group B continuously increased. After one and eight weeks, but not after twelve weeks, the maximal walking distances were significantly longer in group A than in group B. At no point were there significant intergroup differences in terms of painfree walking distance. The data suggest that pentoxifylline is clinically effective in claudicants even when given in addition to exercise. The benefit of drug plus physical therapy compared with exercise alone could be observed mainly in the first weeks of treatment and may wear off during long-term therapy.
Blood rheology after LDL apheresis using dextran sulfate cellulose absorption--a case report.
The authors describe a thirty-eight-year-old woman with familial hypercholesterolemia treated by dextran sulfate cellulose adsorption apheresis. This technique and the selective extracorporeal LDL cholesterol elimination by immunoabsorption or heparin-induced precipitation not only dramatically decrease blood lipids but also result in a marked improvement in the rheologic profile. It is suggested that the amelioration of blood rheology by LDL apheresis may represent the cause for the early clinical improvement felt by most patients with severe coronary heart disease and hypercholesterolemia.
Lovastatin alters blood rheology in primary hyperlipoproteinemia: dependence on lipoprotein(a)?
As part of a randomized, single-blind, comparative study evaluating the efficacy of lovastatin and bezafibrate retard in the treatment of primary hypercholesterolemia, hemorheologic parameters (whole blood viscosity, hematocrit, plasma viscosity, red blood cell aggregation and deformability, and fibrinogen) were studied in 35 patients. Whole blood viscosity and plasma viscosity improved significantly after 3 months of treatment with lovastatin, whereas other hemorheologic variables remained unchanged. Stratifying 24 patients by their lipoprotein Lp(a) levels showed that in those with low Lp(a) (less than or equal to 25 mg/dL) high-density lipoprotein cholesterol increased and red blood cell aggregation as well as deformability decreased considerably, whereas in the group with high Lp(a) levels (greater than 25 mg/dL), the opposite behavior was observed. Treatment of primary hypercholesterolemia with lovastatin may not only reduce the risk for atherosclerotic complications by its pronounced decrease of low-density lipoprotein cholesterol, but also may favorably alter blood rheology, and may decrease insudation of plasmatic components into the arterial wall and improve tissue perfusion, in particular on the microcirculatory level. The possible relevance of Lp(a) levels for the hemorheologic effects of lovastatin remains to be elucidated.
Sex hormones and epididymal sperm parameters in rats following sub-chronic treatment with hexavalent chromium.
Testicular atrophy and reduced epididymal sperm count are known to occur after i.p. administration of high doses of hexavalent chromium to rats. The effect of 0.5 mg kg-1 hexavalent chromium injected i.p. 5 d a week for 8 weeks was investigated in male Wistar rats. A significant reduction in epididymal sperm motility was found at the end of the exposure period. The reduction was reversed after an unexposed period of a further 8 weeks. In addition, a decrease in serum testosterone and an increase in FSH were found at the end of the exposure period. The results indicate that a number of mechanisms may be involved in the deleterious effects of chromate on male fecundity.