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D Seidel

Publications and source records attributed to D Seidel.

At least 145 records · Page 8Linked to original sources
PubMed1991

The HELP-system in the treatment of severe hypercholesterolaemia: acute and long-term experience.

The HELP procedure provides a new means of treating high LDL concentrations in severe hypercholesterolemia with the unique additional effect of lowering Lp(a) and fibrinogen. In combination with HMG-CoA-reductase inhibitors a mean interval value of -75% for LDL as compared to the starting concentration may be achieved. The treatment has the advantage that the patient is not exposed to foreign proteins or compounds with attendant immunological problems. It displays a high degree of reproducibility and an almost unlimited capacity guaranteeing a constant therapy independent of the clinic performing the treatment. The first coronary angiographies after 2 years of HELP treatment in over 50 patients (to be reported elsewhere) give support to the hope that regression of coronary heart disease is possible in humans. Further studies and observations should eventually tell us at what level of LDL, Lp(a) and fibrinogen this may be expected. We trust that the clinical benefit of this treatment regimen will be substantial for those patients who have problems in clearing LDL from their plasma pool and who are at the same time sensitive to elevated LDL-levels by the development of premature coronary sclerosis.

Blood Component Removal↗
PubMed1991

Psychosocial and biobehavioral characteristics of hypertensive men with elevated atherogenic lipids.

Epidemiologic studies demonstrated an excess risk of ischemic heart disease (IHD) among individuals who simultaneously exhibit hypertension and elevated atherogenic lipids (coronary high risk (CHR)-status). Yet, relatively little is known about factors which contribute to the development of CHR-status during early and middle adulthood. The present study explores the role of selected biobehavioral and psychosocial factors in explaining CHR-status using data from a prospective 6.5 years investigation of a cohort of 416 middle-aged (40.8 +/- 9.6 years) male blue-collar workers. Multivariate logistic regression analysis shows that overweight (odds ratio (o.r.) 4.14), smoking (o.r. 2.19), low promotion prospects at work (o.r. 2.71), competitiveness at work (o.r. 2.79) and feelings of sustained anger (o.r. 5.41) independently contribute to the explanation of CHR-status. Furthermore, the operational definition of CHR-status is validated by estimating its power in predicting IHD incidence in the study cohort. In conclusion, co-manifestation of hypertension and elevated lipids is more likely to exist among those blue-collar men who exhibit distinct work-related characteristics in addition to established biobehavioral risks such as overweight and smoking. In view of the high prevalence of CHR-status and of IHD among men in the lower socio-economic strata this finding is also of interest for health policy.

Adult↗
PubMed1991

Complement activation and depletion during LDL-apheresis by heparin-induced extracorporeal LDL-precipitation (HELP).

The heparin-induced extracorporeal elimination of low density lipoproteins (LDL) is a well-established clinical procedure to markedly reduce cholesterol levels. The biocompatibility of this artificial filter system (HELP) was investigated by quantitation of representative complement proteins within the extracorporeal circuit using established ELISA procedures, based on monoclonal antibodies recognizing exclusively either native (C6, C7) or activated proteins (act.C3, C5a, TCC). HELP was found to be a self-limiting extracorporeal system with respect to complement activation, since act.C3 and TCC, generated mainly at the plasma filter, were partially adsorbed to the following HELP specific filters to concentrations which were lower than those obtained before the plasma filter. C5a, which increased 14.5-fold at the plasma filter was not eliminated by the following filters; however, elevated levels were not found in the patients at the end of apheresis and no leucocytopenia was observed.

Adult↗
PubMed1991

The HELP-LDL-apheresis multicentre study, an angiographically assessed trial on the role of LDL-apheresis in the secondary prevention of coronary heart disease. I. Evaluation of safety and cholesterol-lowering effects during the first 12 months. HELP Study Group.

Fifty-one patients with coronary heart disease (CHD) and LDL-cholesterol levels greater than or equal to 200 mg dl-1 despite diet and drug therapy have been recruited into an angiographically controlled, multicentre, two-year study to evaluate HELP-LDL-apheresis in the secondary prevention of CHD. There were five drop-outs in the first year and 46 patients completed one year of therapy. An average of 2.791 of plasma was treated per patient every 7.7 days. Treatment was well tolerated and the incidence of side effects was small (2.9% of treatments). Mean pre-/post-apheresis LDL-cholesterol levels decreased from 283/120 mg dl-1 at baseline to 207/78 mg dl-1 and 203/76 mg dl-1 after 6 and 12 months, respectively. Mean pre-/post-apheresis HDL-cholesterol levels rose significantly over the course of therapy from 40.5/36.6 mg dl-1 to 44.8/39.7 mg dl-1 and 48.2/41.3 mg dl-1 after 0, 6 and 12 months, respectively. No major derangement of pre-apheresis haemostasis nor of haematological or clinical chemical parameters had occurred after 12 months of treatment. The data from this study support the feasibility of HELP-LDL-apheresis as an adjunctive therapy for lowering cholesterol levels in CHD patients refractory to cholesterol-lowering drugs while substantially improving the HDL/LDL ratio.

Adult↗
PubMed1991

[Lipoprotein (a)].

Explore the source record for details and available documents.

Arteriosclerosis↗
PubMed1991

Contribution of the apo[a] phenotype to plasma Lp[a] concentrations shows considerable ethnic variation.

Apolipoprotein[a] polymorphism has been investigated by sodium dodecyl sulfate polyacrylamide (5.37%) gel electrophoresis and immunoblotting using a standardized sample load in four ethnic groups: German, Ghanaian, Chinese, and San (Kalahari Bushmen). A total of 10 different apparent molecular weight (Mr) polymorphs, designated 1 to 10 with increasing Mr, were detected in greater than 99% of all individuals tested (German, 99%; Ghanaian, 99%; Chinese, 100%; San 100%). A null allele is therefore at most an infrequent variant in all populations. Polymorphs 6-10 were common to all four populations, while polymorphs 1-5 appeared to be relatively rare variants not universally detected in each group in the present study. The Chinese had the highest proportion of double-band phenotypes and the observed frequencies were not significantly different from those expected according to simple Mendelian inheritance, whereas the observed apo[a] phenotype distributions of the other three groups did not concur with those expected for Hardy Weinberg equilibrium. The German and Ghanaian groups displayed similar distributions of apo[a] phenotypes while the Chinese and San had significantly higher frequencies of polymorphs 9 and 10. Mean plasma Lp[a] concentrations in Ghanaians (36.2 +/- 31.5 mg/dl) were almost 2-fold greater than in Germans (18.7 +/- 23.1 mg/dl) and ca 1.65-fold greater than in either Chinese (22.9 +/- 18.3 mg/dl) or San (21.1 +/- 19.3 mg/dl). A strong inverse correlation was observed between apo[a] Mr and plasma Lp[a] concentration in Germans but this was much less pronounced in Ghanaians. While the mean plasma Lp[a] levels associated with polymorphs 1-6 were similar in both Germans (43.4 +/- 30.0 mg/dl) and Ghanaians (49.2 +/- 37.6 mg/dl), those Ghanaians with any combination of the polymorphs 9 and 10 had an almost 3-fold greater mean plasma Lp[a] level (20.6 +/- 11.3 mg/dl) than their German counterparts (7.8 +/- 5.7 mg/dl). It is therefore apparent that: 1) differences in apo[a] allele frequencies are not primarily responsible for differences in Lp[a] levels between populations; and 2) the greatest ethnic variation is observed in plasma Lp[a] concentrations associated with the high molecular weight apo[a] polymorphs.

Africa↗
PubMed1990

Effects of long-term treatment with simvastatin on plasma lipids and lipoproteins in patients with primary hypercholesterolemia.

We investigated long-term hypolipidemic effects and clinical safety of simvastatin, a new competitive inhibitor of 3-hydroxy-methylglutaryl coenzyme A reductase in 24 patients with familial and non-familial hypercholesterolemia. Patients received up to 40 mg simvastatin for a period of 30 months. Significant decreases were noted in plasma cholesterol (30%), plasma triglycerides (25%), very low density lipoprotein-cholesterol (26%), and low density lipoprotein-cholesterol (40%), whereas an increase in plasma high density lipoprotein-cholesterol (11%) was observed. Furthermore, the percentage decrease in plasma low density lipoprotein cholesterol was independent of individual baseline concentrations. Simvastatin did not alter the composition of low density lipoproteins or high density lipoproteins. The percentage decrease in total plasma and low density lipoprotein-cholesterol was independent of apoprotein E isoforms and low density lipoprotein-receptor activity as assayed in cultured fibroblasts. The drug therapy was well tolerated and clinical examinations revealed no adverse effects. Clinical chemistry indices and hematological, as well as endocrinological parameters remained within normal limits and ranges.

Adult↗
PubMed1990

Low-density lipoprotein plasmaphaeresis with and without lovastatin in the treatment of the homozygous form of familial hypercholesterolaemia.

A 7-year-old girl with homozygous familial hypercholesterolaemia and plasma low-density lipoprotein(LDL)-cholesterol levels of 820 mg/dl (21.2 mmol/l) and progressive xanthomata was treated with heparin extracorporeal low-density lipoprotein precipitation (HELP) to lower her plasma LDL. On weekly HELP treatment she maintained her pre-HELP treatment LDL-cholesterol levels at 409 mg/dl (10.6 mmol/l). The long-term HELP treatment was well tolerated and led to regression of her xanthomata. Subsequently, lovastatin [Mevacor; Merck Sharp & Dohme, Westpoint, Pa., USA (20 mg/day)] was added to the regimen, causing a further 20% decrease in her pre-HELP treatment plasma LDL-cholesterol levels. Lovastatin alone did not sufficiently lower her plasma LDL and could not replace the weekly HELP therapy. Our data show that lovastatin is an effective adjunctive therapy for lowering plasma LDL-cholesterol in a homozygous patient, once plasma LDL levels have already been lowered by regular HELP treatment.

Child, Preschool↗
PubMed1990

Low status control, high effort at work and ischemic heart disease: prospective evidence from blue-collar men.

An inverse relation between socio-economic class and occurrence of ischemic heart disease (IHD) in advanced societies is an often replicated finding from empirical studies. Yet, the processes which produce these effects remain an open question. One promising explanation concerns the prevalence of stressful working life, especially of distinct 'job strain' occupations. Based on these considerations, we develop a refined concept of work-related socio-emotional distress which considers a mismatch between high workload and low control over occupational status (e.g. job insecurity, poor promotion prospects, status inconsistency) as crucial distress-provoking conditions. Moreover, we assume that the effect of this condition on IHD risk is substantially increased by the presence of a distinct individual pattern of coping with work demand ('need for control'). Based on data from a 6.5 years prospective study on IHD incidence (n = 21) in a cohort of 416 middle-aged blue-collar men this concept is tested using logistic regression analysis. Results indicate that status inconsistency [multivariate odds ratio (o.r.): 4.4], job insecurity (o.r. 3.4), work pressure (o.r. 3,4) and 'need for control' (o.r. 4,5) independently predict IHD occurrence after adjusting for major confounding somatic and behavioral coronary risk factors. In conclusion, a refined model of work-related socio-emotional distress substantially contributes to the explanation of high IHD incidence among blue-collar men.

Adaptation, Psychological↗
PubMed1990

Receptor mediated uptake of apo B and apo E rich lipoproteins by human glomerular epithelial cells.

Various pathological disorders are accompanied by the deposition of lipids into glomerular cells. To gain insight into these disorders, it is essential to know if glomerular cells possess lipoprotein receptors. We therefore characterized the activity of lipoprotein receptors in cultured epithelial cells of the human glomerulus. Podocytes were chosen as they are directly exposed to lipoproteins in pathological states like in glomerular proteinuria (such as, nephrotic syndrome). Isolated human glomeruli (purity greater than 95%) were incubated in buffered RPMI 1640 medium supplemented with 20% heat-inactivated fetal bovine serum at 37 degrees C and 5% CO2. Outgrowing cells were vimentin and keratin positive. Monolayer cultures of human glomerular epithelial cells upon incubation in lipoprotein deficient serum for 48 hours expressed a receptor-dependent uptake of lipoproteins. These cells showed about 10% of the maximal capacity for LDL uptake as compared to fibroblasts; however, the Km values for binding, internalization and degradation were similar in the cultures of glomerular epithelial cells and fibroblasts. The Km values for degradation of LDL, chylomicron remnants, beta-VLDL from cholesterol-fed rabbits and VLDL from familial LCAT-deficiency patients were 14.2, 4.9, 2.9, 4.5 micrograms protein/ml medium, respectively, for glomerular epithelial cells. The avid uptake of 125I-labeled apo E-containing lipoproteins was further substantiated by their poor displacement by a 25-fold excess of unlabeled LDL and their ability to down regulate the apo B,E receptor activity. LDL as well as beta-VLDL were able to suppress the incorporation of 14C acetate into sterols and to stimulate 3H-cholesterylester formation. These experiments show that cultured glomerular epithelial cells express lipoprotein receptor activity. Plasma concentrations of apo E-containing lipoproteins are increased in certain renal diseases (such as, nephrotic syndrome); these lipoproteins could be rapidly removed by glomerular epithelial cells and lead to lipid deposition in glomeruli.

Apolipoproteins B↗
PubMed1990

[Defective remnant clearance as a risk factor for coronary heart disease].

We investigated the metabolism of postprandial lipoproteins in four male patients who suffered from premature (less than 60 years) angiographically proven coronary heart disease. They had normal to low plasma total and low density lipoprotein cholesterol levels. Other risk factors were absent. Using the vitamin A fat loading test we were able to show that the clearance of chylomicron remnants was delayed compared to three healthy control subjects. It has been suggested that these postprandial lipoproteins may be atherogenic. Our data strongly favour the concept that defective removal of postprandial lipoproteins leads to the development of coronary heart disease in these patients.

Aged↗
PubMed1990

Pravastatin--ocular side effects after a two year follow-up?

Pravastatin, a new HMG-CoA-reductase inhibitor, was administered to hypercholesterolemic 14 patients with coronary heart disease for a period of two years. This drug reduces the plasma LDL-cholesterol concentrations approximately 30-40%. No development of cataracts or other ocular side effects could be observed during this two year follow-up.

Aged↗
PubMed1990

Heterogeneity of human lipoprotein Lp[a]: cytochemical and biochemical studies on the interaction of two Lp[a] species with the LDL receptor.

Human Lp[a] can be fractionated into two species with different affinities for lysine-Sepharose. Forty to 81% of the total Lp[a] in the density fraction 1.055-1.15 g/ml from five individuals was retained by this affinity column. The remaining unretained Lp[a] species with no apparently functional lysine binding site was similar to the retained species in its electrophoretic mobility, lipid, protein, and apolipoprotein composition, and the heterogeneity was not related to apo[a] size polymorphism. Interaction of the two species with the low density lipoprotein (LDL) receptor was studied in human fibroblasts. Using gold-labeled lipoproteins and an immunochemical procedure, both Lp[a] species could be located in clusters on the cell surface, but the extent of labeling was far lower than that seen with LDL. Both Lp[a] variants were less effective than LDL in 1) down-regulation of LDL-receptor activity; 2) suppression of cellular sterol synthesis; and 3) stimulation of cholesteryl ester formation in human fibroblasts. Although degradation of both species of Lp[a] by the perfused rat liver was stimulated after estrogen induction of hepatic LDL-receptor activity, the stimulation amounted to only a quarter of that seen with LDL. The heterogeneity of Lp[a] with respect to the ability to bind epsilon-aminocarboxylic acid will need to be considered in studying the physiological role of this lipoprotein. Both Lp[a] species exhibited a similar interaction with the LDL-receptor in vitro, and confirmed previous investigations that Lp[a] is only a poor ligand for the LDL-receptor.

Affinity Labels↗
PubMed1990

The HELP system: an efficient and safe method of plasma therapy in the treatment of severe hypercholesterolemia.

The HELP procedure provides a new means of very efficiently treating high LDL concentrations in severe hypercholesterolemia with the additional effect of lowering Lp(a) and fibrinogen while HDL are increased during long-term treatment. The HELP treatment also significantly improves plasma viscosity, erythrocyte aggregation and erythrocyte filtration. Overall treatment tolerance is very good, and no major complications have been observed after approximately 10,000 single treatments in 155 patients--some of them treated for more than three years. In combination with HMG-CoA reductase inhibitors, a mean interval value of--75% for LDL as compared to the starting concentration may be achieved. The treatment has the advantage that the patient is not exposed to foreign proteins or compounds with attendant immunological problems. It displays a high degree of reproducibility and an almost unlimited capacity, guaranteeing a constant therapy independent of the clinic performing the treatment. We trust that the clinical benefit of this treatment regimen will be substantial for those patients who have problems in clearing LDL from their plasma pool and who are at the same time sensitive to elevated LDL levels by the development of premature coronary sclerosis.

Adult↗
PubMed1990

[Description of a special form of postprandial hyperlipidemia: possible cause of premature coronary heart disease].

We have studied the metabolism of post-prandial lipoproteins in four male patients who suffered from premature (less than 60 years) angiographically proven coronary heart disease. They had normal to low total and low density lipoprotein cholesterol levels. Other risk factors were absent. Using the vitamin A fat loading test we were able to show that the clearance of chylomicron remnants was delayed compared to three healthy control subjects. Since these postprandial lipoproteins have been implicated in atherogenesis, we conclude that this defect contributed to the development of coronary heart disease in these patients.

Adult↗
PubMed1990

[Maximal therapy of hypercholesterolemia in coronary heart disease].

Extracorporeal procedures to eliminate LDL from plasma now allow us to drastically lower the plasma LDL-concentrations to virtually every desired level. In a new therapeutic approach the combination of HMG-CoA reductase inhibitors with an LDL/fibrinogen apheresis procedure (the HELP-system) was evaluated in hypercholesterolemic CAD-patients. HELP treatment alone can lower the mean plasma LDL-cholesterol by about 50-60%, HMG-CoA reductase inhibitor therapy reduces the LDL-cholesterol by about 40%. The combination of both treatments resulted in a lowering of mean LDL-cholesterol to about 80% of baseline values. Improvement of blood rheology by lowering plasma viscosity and inhibiting erythrocyte aggregation became apparent. No relevant adverse effects were noted over a period of two years. This therapeutic strategy for maximal LDL-cholesterol lowering may be useful in secondary prevention of coronary heart disease in hypercholesterolemic patients if plasma LDL-C cannot be reduced by diet and drug treatment to desirable plasma levels (LDL-cholesterol less than 120 mg/dl). Preliminary data show an improvement in the symptoms of our CAD-patients treated with this combined therapy. Furthermore, within the near future a combined HELP and dialysis unit will be available for patients with terminal renal insufficiency and progressive atherosclerosis.

Adult↗