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Biomedical subjects

D Seidel

Publications and source records attributed to D Seidel.

At least 163 records · Page 9Linked to original sources
PubMed1989

[Risk of myocardial infarct in 40 to 60-year-old males in relation to potential risk factors of atherosclerosis. Intermediate evaluation of the Göttingen risk, incidence and prevalence study following a 5-year observation period].

The main part of the Göttingen risk, incidence and prevalence study (GRIPS) is a prospective cohort-study (GRIPS-project B). In 1982 about 6,000 male subjects aged 40-60 years underwent an extensive, baseline examination. The incidences of death and disease are being recorded in this collective by regular follow-up investigations. A five-year observation period has now been completed for more than 95% of the original study participants. During this period 107 subjects, who had no symptoms of atherosclerotic diseases in 1982, developed fatal or non fatal myocardial infarction (MI). In the present evaluation this incidence group is compared to those study participants, who remained free of atherosclerotic diseases until December 1986 (reference group: n = 5160). The results indicate that LDL-cholesterol is the predominant predictor of MI-risk among all variables investigated. Additional risk factors of significance were as follows (in the rank order of their importance): positive family history of MI, hyperglycemia, low HDL-cholesterol, increased levels of triglyceride-rich-lipoproteins, hypertension, cigarette-smoking. For the most important risk-factor, LDL-cholesterol, 190 mg/dl seem to be a useful threshold value for therapeutic intervention according to the present data from GRIPS-project B. However, if additional risk-factors or definitive coronary artery disease are present, LDL-cholesterol levels below 140 mg/dl should be the therapeutic aim.

Adult↗
PubMed1989

Luminescence in the study of lipid metabolism.

Using bioluminescence assays for glycerol, free fatty acids, beta-hydroxybutyrate and lactate, we were able to perform complex studies of human energy and lipid metabolism both in serum samples in vivo and in isolated fat cells in vitro. These studies would have been impossible without reliable, specific and highly sensitive luminescence methods. Oxidatively modified low density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis. Adaptation of a chemiluminescence assay for lipid hydroperoxides to LDL isolated by specific precipitation from serum makes it possible to measure LDL oxidation in vivo. Cell dependent chemiluminescence was used to investigate whether receptor mediated endocytosis of LDL by macrophages leads to oxygen radical production in these cells. No activation of the membrane NAD(P)H oxidase was observed.

Adipose Tissue↗
PubMed1989

One-year MR imaging follow-up of patients with multiple sclerosis under cortisone therapy.

Twenty patients with relapsing/remitting course of MS were studied four times with MR imaging over the course of one year. First MR was undertaken during the acute relapse, afterwards patients were given cortisone therapy for four to six weeks. The second MR study followed 4-6 weeks after the first, the patients at this time being in remission. The third MR study was carried out 4 months after the first, the last scan one year after the first. The total number of lesions varied, though not greatly, over the whole follow-up, but there was an influence of the clinical course of MS on the pattern of lesions in MR imaging, mostly in respect to the number of confluences and the size of the lesions. Follow-up over one year showed that the inflammatory process produced an increase in the number of plaques, independent of the fact that most patients stayed in remission. A delayed effect of the cortisone therapy on the size, number, and confluence of plaques is suggested whilst clinical signs improved in most cases immediately after the beginning of drug therapy. Independent of the clinical course of the disease in some cases plaques previously seen vanished and others appeared in one and the same examination.

Adult↗
PubMed1989

Enhanced procoagulatory activity (PCA) of human monocytes/macrophages after in vitro stimulation with chemically modified LDL.

In cultured human monocytes/macrophages, surface expression of procoagulatory activity (PCA) was induced by chemically modified LDL (acetyl-LDL and MDA-LDL) in a dose- and time-dependent manner. Maximum PCA (30-fold increase) was detected after 24 h of culture with modified LDL at doses of 25-750 micrograms protein/ml. Using factor VII deficient human plasma and phospholipase C this PCA was identified as tissue thromboplastin activity (factor III). These results suggest a further atherogenic potential for modified LDL through stimulation of the conversion of fibrinogen to fibrin in the atheromatous lesion.

Blood Coagulation Factors↗
PubMed1989

Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin-induced extracorporeal LDL precipitation (HELP).

Heparin-induced Extracorporeal LDL-Precipitation (HELP) is an effective procedure for the elimination of both plasma LDL and fibrinogen. In 10 adult patients with severe type II hyperlipoproteinemia, a single HELP treatment of 3 1 plasma led to an acute decrease in the average plasma viscosity (PV) from 1.30 to 1.1 mPas. At the same time, an even more marked decrease in the mean erythrocyte aggregation rate from a pathological value of 7.9% to a value of 3.7% (normal range less than 5%) was observed. Long-term studies on five patients demonstrated a lasting improvement in these two haemorheological variables. The acute rheological changes were also accompanied by an improvement in polarographically determined muscle oxygen tension. Mean oxygen tension values measured in both the m.biceps brachii and the m.tibialis anterior in five patients before and after a single HELP treatment increased from 30 +/- 4 to 37 +/- 7 mmHg and from 27 +/- 2 to 31 +/- 3 mmHg respectively. These results may provide an explanation for the rapid improvement in patients' clinical symptoms such as angina pectoris and in stress electrocardiogram which have been observed during HELP therapy.

Adult↗
PubMed1989

Effect of HELP-LDL-apheresis on serum concentrations of human lipoprotein(a): kinetic analysis of the post-treatment return to baseline levels.

In addition to LDL, Lp(a) can be quantitatively eliminated from plasma in an extracorporeal LDL-apheresis procedure based on precipitation with heparin at pH 5.12. The rates of return of post-apheresis Lp(a) and LDL-cholesterol concentrations to baseline levels were investigated in six individuals with familial hypercholesterolaemia (one homozygote, five heterozygote) and one normolipaemic individual. The first-order disappearance constants (kappa) were derived for LDL and Lp(a) according to Apstein et al. The kappa values for LDL in the homozygous FH and the normolipaemic individual were 0.082 and 0.43 respectively while the heterozygous FH patients had kappa values intermediate between the two (median 0.231; range 0.116-0.261). The first-order disappearance constants of Lp(a) did not correlate with those of LDL. The homozygous FH and normolipaemic individuals had Lp(a) kappa values of 0.158 and 0.199 respectively; the corresponding values in the heterozygous FH patients were: median 0.142; range 0.045-0.179.

Adult↗
PubMed1989

Characterization of five mouse monoclonal antibodies to apolipoprotein[a] from human Lp[a]: evidence for weak plasminogen reactivity.

We describe the development of five murine monoclonal antibodies (14A12, 39A1, 53A9, 73A7, and 128A6) specific to human apolipoprotein[a] (Mr approximately 570,000), and their characterization by a number of procedures including cotitration, competition and inhibition enzyme-linked immunosorbent assays (ELISA), immunoblotting of native lipoproteins and of SDS-solubilized apolipoproteins electrophoresed in polyacrylamide gels, and dot immunobinding assays. The patterns of immunoreactivity of these antibodies were similar. Each reacted in ELISA assays and upon electroimmunoblotting with purified apo[a], with apo[a] liberated by reduction of Lp[a], and with delipidated Lp[a] solubilized in SDS, but by contrast, they reacted with native Lp[a] to a significant degree only upon electroimmunoblotting. No reactivity was seen with LDL-apoB-100 or with other apolipoproteins. The cross-reactivity of these antibodies with the homologous protein, plasminogen, was examined by comparison of the amount of plasminogen or apo[a] required for 50% inhibition of antibody binding to apo[a], and by an ELISA assay. The inhibition assay showed reactivity with plasminogen to be 37- to 50-fold lower than with apo[a], while dot immunobinding showed the lower limit of detection of plasminogen and of apo[a] to be approximately 320 and 31 micrograms, respectively. In an ELISA sandwich assay based on monoclonal antibodies LHLP-1, 14A12, and 53A9, the lower limit of Lp[a] detection (approximately 1 ng/ml protein) was about 100-fold less than that of plasminogen. Chemical modification of apo[a] revealed a significant contribution of arginine residues to the epitopes of 14A12, 39A1, and 53A9. Modification of cysteine residues with iodoacetamide was without effect, thereby distinguishing these antibodies from LHLP-1. Each antibody reacted with the six major size forms of apo[a] (Mr approximately 450,000-750,000) in immunoblots of human sera electrophoresed in SDS-polyacrylamide gels. Marked heterogeneity in apo[a] phenotype was detected and both single and double band phenotypes were observed in a randomized study. Cotitration and competition binding studies showed varying degrees of interaction between all five epitopes, with the exception of 128A6 which appeared to be independent of 39A1 and 53A9 (and vice versa). These data suggest that our five monoclonal antibodies recognize epitopes on apolipoprotein[a] that are exposed and accessible on the native Lp[a] particle. We conclude that our monoclonal antibodies recognize a specific region of apo[a], and that this region undergoes a conformational change upon adsorption of Lp[a] to plastic thereby diminishing epitope recognition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Metyrapone decreases the glutathione concentration in liver and kidney.

A single dose of 7.5 mg/100 g b.wt. metyrapone, intraperitoneally, decreased the concentration of reduced (GSH) and oxidized (GSSG) glutathione in the liver and kidney of female Wistar rats for approximately 4-5 h. The ratio between GSSG and GSH was not affected in the kidney but is decreased in the liver.

Animals↗
PubMed1989

Induction of glomerulosclerosis by dietary lipids. A functional and morphologic study in the rat.

Clinical and experimental data indicate that glomerular function and morphology may be influenced by plasma lipids. In familial lecithin-cholesterol-acyltransferase (LCAT) deficiency and in Fabry's disease, lipids accumulate in glomeruli and are assumed to induce sclerosis. The present study was undertaken to examine if dietary lipids could exert effects on the glomeruli of normal, unilaterally nephrectomized rats, and of rats with two-kidney, one clip (2-K,1C) hypertension. In rats with two kidneys on a diet rich in fat and cholesterol, cholesterol concentrations in very low density lipoproteins increased. In these rats the number of glomeruli with sclerotic foci was significantly higher than in rats on a low fat, cholesterol free diet. After 6 months on the diet the percentage of glomeruli with sclerosis (SC) was 13.2 +/- 4.1 (N = 9) in rats with a cholesterol diet and 1.8 +/- 0.6 (N = 11) in control rats (p less than 0.05). The fat and cholesterol diet exacerbated glomerular lesions in the remnant kidney model of uninephrectomized rats. The sclerosis in rats with only one kidney was 38.2 +/- 9.5 (N = 6) on a cholesterol diet compared with 8.7 +/- 3.0 (N = 6) in control rats after 6 months (p less than 0.05). After 3 to 4 months on a fat rich diet cholesterylester was increased in isolated glomeruli. The composition of the dietary lipids influenced the development of glomerular lesions. A linseed oil diet that is rich in unsaturated fatty acids, especially linolenic acid, did not cause major plasma lipid abnormalities and was accompanied by a low sclerosis (1.2 +/- 0.3; N = 9) for rats with two kidneys. In rats with chronic 2-K, 1C hypertension the percentage of glomeruli with partially sclerosed tufts in the unclipped kidney was significantly higher on a fat and cholesterol diet (F) than on a control diet (N) (SC: diet F 31.0 +/- 4.0, N = 13; diet N 12.2 +/- 2.6, N = 12; P less than 0.05). In the clipped kidney, protected against the arterial hypertension, only an increased number of glomeruli with mesangial expansion was noted in rats with the cholesterol diet. Glomerular hemodynamic factors seem to play an important pathogenetic role in the induction of glomerular sclerosis by a lipid rich diet. The fact that dietary lipids can aggravate glomerular lesions in states of arterial hypertension and nephron loss may have implications for the progression of renal disease in humans.

Animals↗
PubMed1988

Acute and long-term effects of low-density lipoprotein apheresis on the serum concentrations of vitamins E and A.

Serum alpha-tocopherol and retinol concentrations were followed in four heterozygous adults and one homozygous child with familial hypercholesterolemia being treated by regular low-density lipoprotein (LDL) apheresis. Approximately 50% of plasma alpha-tocopherol was eliminated during a single apheresis procedure in the heterozygous adults, while a complete elimination of this vitamin along with LDLs was observed in the homozygous child. Absolute losses of alpha-tocopherol amounted to 13.4-22.5 mg/apheresis and are equivalent to the recommended dietary intake for 1.5 to 2 days. Despite these losses, no changes were observed either in serum alpha-tocopherol levels or in the ratio of alpha-tocopherol/total serum lipids after 12 months regular apheresis treatment. Serum retinol concentrations only showed a small decrease on apheresis, there being apparently no specific elimination of this vitamin. The absolute losses ranged from 42-422 micrograms/apheresis and were, therefore, much lower than the recommended dietary intake of the equivalent of 1500 micrograms retinol/day. It is concluded that no extra supplementation of these vitamins is required during LDL-apheresis therapy, although it may be advisable to monitor vitamin E status in patients on long-term, intensive therapy.

Adult↗
PubMed1988

Removal of low-density lipoproteins (LDL) and fibrinogen by precipitation with heparin at low pH: clinical application and experience.

The clinical application of a new extracorporeal procedure (HELP) for the selective elimination of low-density lipoproteins and fibrinogen by heparin precipitation at acid pH is described. Plasma, obtained by filtration of whole blood through a 0.2 micron filter is continuously mixed with an equal volume of an acetate buffer (pH 4.85) containing heparin. After removal of the precipitated heparin complex by filtration, excess heparin is adsorbed to a specially developed filter, and the clear plasma filtrate is subject to bicarbonate dialysis/ultrafiltration to restore physiologic pH and remove excess fluid. The calculated efficiency for the elimination of low-density lipoproteins and fibrinogen from plasma by HELP is 100% and is therefore comparable to conventional plasmapheresis. However, the HELP system shows a high degree of specificity, with over 80% of total protein being returned to the patient. A total of over 350 treatment procedures have now been performed. Patient compliance and acceptance have been excellent, and no major complications have been observed. The system is therefore suitable for the treatment of severe hyper-beta-lipoproteinemia; its use for the treatment of coronary heart disease is currently under investigation in a prospective multicenter study in which treatment efficiency will be controlled by coronary angiography on 45 patients treated with HELP over a period of 2 years.

Blood Component Removal↗
PubMed1988

Atherogenic risk in men suffering from occupational stress.

Blue-collar workers suffering from chronic occupational stress exhibit significantly higher values of an atherogenic index (ratio between low density and high density lipoprotein cholesterol assessed by quantitative lipoprotein electrophoresis) as compared to men exposed to less stress at work. Chronic occupational stress is defined by interactions of objective (job instability, shift work) and subjective (perceived job insecurity, perceived increase of work load) indicators as assessed by structured interviews. Findings from a prospective epidemiologic study on 416 middle-aged men at entry covering a 2-year period of observation hold true after controlling for several confounding factors such as body weight, age, cigarette smoking and chronic alcohol consumption. Results are in line with experimental animal studies on the influence of chronic social stress on the development of atherosclerosis.

Adolescent↗
PubMed1988

Lipid metabolic changes during hormonal treatment of endometriosis.

Three groups of patients with pelvic endometriosis were treated with medroxyprogesterone acetate (MPA) 50 mg/day (n = 10), lynestrenol (LYN) 10 mg/day (n = 25) and danazol (DAN) 600 mg/day (n = 25) respectively. Total cholesterol, triglycerides, alpha-lipoprotein, prebetalipoprotein, beta-lipoprotein cholesterol, high-density (HDL) and low-density (LDL) lipoprotein and apolipoprotein A1 and B concentrations were determined before treatment and after 3 and 6 mth of therapy. Whereas lipid, lipoprotein and apolipoprotein levels did not change in the MPA group, the patients on LYN and in particular those on DNA showed marked changes in lipoportein patterns. Alpha-lipoprotein, HDL and apolipoprotein A1 levels fell, while beta-lipoprotein, LDL and apolipoprotein concentrations rose, these changes being statistically significant. No alterations were seen in the serum levels of cholesterol, triglycerides or prebetalipoprotein cholesterol. In view of a possible relationship between high LDL and low HDL levels and a risk of accelerated coronary arteriosclerosis in women it was concluded that progestogen-induced alterations in lipoprotein patterns should be avoided as far as long-term treatment is concerned and where additional risk factors are present.

Adult↗
PubMed1988

Relation between renal and hepatic excretion of drugs: X. Excretion of nalorphine in young and adult rats pretreated with hormones or xenobiotics.

Different processes are involved in renal and hepatic excretion of organic anions and cations. In contrast to our knowledge of anion excretion, information about cation transport in kidney and liver is relatively scarce. In this study, the elimination of nalorphine was investigated to characterize the relation between renal and hepatic excretion of organic cations. Nalorphine is excreted effectively both via kidney and liver. However, its hepatic excretion dominates in adult rats. In young, 20-day-old animals biliary nalorphine elimination is immature and the excreted amounts are significantly lower. Renal excretion of nalorphine is quite similar in rats of both ages. After bile duct ligation renal excretion of nalorphine increases significantly in adult rats whereas it remains unchanged in young ones. Remarkably, after bilateral nephrectomy hepatic elimination of nalorphine is even diminished in both age groups. In further experiments renal excretion of nalorphine could be stimulated in adult rats after repeated administration of trometamol, triiodothyronine, or dexamethasone; these treatments had no consequences on biliary secretion of nalorphine.

Aging↗
PubMed1988

Comparison of low molecular weight heparin to standard heparin in hemodialysis/hemofiltration.

Low molecular weight (LMW) heparin has been compared to standard unfractionated (UF) heparin in hemodialysis/hemofiltration in a 12 month, randomized study. Seventy patients with end-stage chronic renal failure starting dialysis treatment were randomly assigned to one of two groups treated with either LMW or UF heparin. The LMW and UF heparin doses used produced similar plasma anti-FXa levels, and comparable antithrombotic effectiveness was observed in the two groups as reflected in similar incidences of thrombus formation in the extracorporeal circulation: 1.59% and 1.33% for LMW and UF heparin, respectively. No bleeding complications were seen with either heparin, but significantly (P less than 0.05) fewer erythrocyte concentrates were needed in the LMW heparin patients. Mean factor VIII activities had risen significantly (P less than 0.001) after 12 months in the UF heparin group, whereas they were unchanged in the LMW heparin group. A significant (P less than 0.05) increase in plasma triglycerides was observed in the UF heparin group which was attributable to six (18.8%) of the patients in this group. Triglyceride concentrations remained relatively constant in the LMW heparin group. Post-heparin lipolytic activity, and in particular hepatic lipase activity, was not stimulated to the same extent in the LMW heparin-treated patients as compared to the UF heparin group. We conclude that LMW heparin is a suitable alternative to standard UF heparin for anticoagulation in hemodialysis/hemofiltration therapy. It may offer potential advantages with regard to a lower requirement for erythrocyte concentrates and less derangement of certain metabolic parameters, such as factor VIII, triglycerides and plasma lipase activity.

Blood Coagulation↗