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Biomedical subjects

D Seidel

Publications and source records attributed to D Seidel.

At least 19 recordsLinked to original sources
PubMed1992

[New strategies in treatment of severe hypercholesterolemia in coronary patients: HMG-CoA reductase inhibitors and H.E.L.P.-LDL apheresis].

LDL-cholesterol is the leading risk factor which influences the clinical outcome of patients with preexisting coronary heart disease. Clinical trials show that diet and medication, that lower plasma LDL-cholesterol below 100 mg/dl decrease the rate of recurrent myocardial infarction and can induce regression in patients with coronary heart disease. However, in most cases of severe hypercholesterolemia with plasma LDL-cholesterol concentrations above 220 mg/dl LDL cannot be sufficiently decreased by maximal dietary and pharmacological therapy alone. Today this group of high risk CHD patients can be treated in addition with an extracorporeal procedure to eliminate LDL from the plasma circulation, the H.E.L.P.-LDL-apheresis. This method for selective removal of LDL, lipoprotein(a) and fibrinogen from plasma has been shown to be a clinically safe and very efficient method for the treatment of patients with homozygous familial hypercholesterolemia or CHD patients with severe hypercholesterolemia. Treatments with one week H.E.L.P. intervals revealed a mean reduction of minus 51% for LDL, of minus 45% for Lp(a) and of minus 46% for apo B, while HDL was increased by +12%. Fibrinogen was decreased by minus 46%. Besides the marked reduction of LDL and fibrinogen plasma concentrations the H.E.L.P.-treatment significantly improves hemorheological parameters and increases the oxygen tension in the tissue. We have also investigated the efficiency of a combined therapy, using HMG-CoA reductase inhibitors together with the H.E.L.P.-apheresis. Under this combined treatment, a reduction of the interval LDL-cholesterol levels of 70-80% has been achieved, while Lp(a) and fibrinogen were not further affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Component Removal↗
PubMed1992

Apolipoprotein A-I and apolipoprotein B containing lipoprotein particles in coronary patients treated with extracorporal low density lipoprotein precipitation (HELP).

Evidence for chemical and biological heterogeneity of human plasma lipoprotein density classes has been steadily accumulating over the last 15 years. Furthermore, several recent reports have indicated potential clinical significance of certain lipoprotein subspecies as either atherogenic or antiatherogenic. It is generally accepted that lipid lowering treatments can retard or even reverse development of atherosclerotic lesions. However, very little is known about effects of various lipid lowering treatments on specific lipoprotein particles. The purpose of this study was to explore the effects of heparin induced extracorporal low density lipoprotein precipitation (HELP) on various subspecies of plasma lipoprotein particles defined primarily by their apolipoprotein composition. Using particle specific enzyme immunoassays, the immediate changes in lipoprotein particle profiles were analyzed after a single HELP treatment in 12 patients with angiographically documented coronary artery disease. In a separate group of 6 patients, particles were repeatedly measured over a period of 96 h following a HELP treatment. Single HELP treatment caused an immediate and highly significant decrease (67%) in the concentration of simple lipoprotein particles containing apolipoprotein B (apo B) as a sole apolipoprotein (LP-B). Various subspecies of complex particles containing apo B and other apolipoproteins (Lp-B-complex) were also decreased although to a lesser degree (44-53%). HELP treatment caused an insignificant, 3% decrease of lipoprotein particles containing apo A-I but no apo A-II (Lp-A-I) and a 6% decrease in the concentration of particles containing both apo A-I and apo A-II (Lp-A-I:A-II). During the 96-h period following HELP treatment various apo B containing particles recovered at different rates in different patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Apolipoprotein A-I↗
PubMed1992

Actions of lipoproteins in cultured human mesangial cells: modulation by mitogenic vasoconstrictors.

Recent studies have suggested that hypercholesterolemia may aggravate glomerulosclerosis. Mesangial cells actively participate in this process. To elucidate mechanisms by which lipids act on human mesangial cells (HMC), we measured the receptor-specific uptake of apolipoprotein (Apo) B- and Apo B- and E-containing lipoproteins in the presence and absence of growth factors and studied the growth-related mechanisms in HMC after exposure to low-density lipoprotein (LDL). Human LDL and very low density beta-lipoprotein (beta-VLDL) isolated from cholesterol-fed rabbits were bound, internalized, and degraded by a receptor-specific mechanism (dissociation constants for degradation LDL 30.0 and for beta-VLDL 4.1 micrograms protein/ml medium). Maximal capacities were 30-50% of those of human fibroblasts. Acetylated and copper-oxidized LDL were not taken up specifically, suggesting no active scavenger-receptor activity. Preexposure to endothelin-1 (5 x 10(-7) M) and platelet-derived growth factor (PDGF A, B, 83 x 10(-12) M) for 16 or 15 h, respectively, doubled the uptake of LDL by HMC. In addition, PDGF synergized with LDL in stimulating DNA synthesis. Exposure of HMC to LDL resulted in a transient elevation of mRNA that encodes c-fos and c-jun, with a maximal effect seen after 30-60 min. In addition, PDGF A- and B-chain mRNAs were transiently elevated, peaking at 3 h in response to LDL (25 micrograms protein/ml medium) and continued to increase in a concentration-dependent manner (25-75 micrograms protein/ml medium). These data demonstrate that HMC take up lipoproteins via a receptor-specific mechanism with a high affinity for Apo E-containing lipoproteins which are often found in plasma of patients with renal disease. Vasoconstrictor and mitogenic peptides enhance lipoprotein receptor activity and have a synergistic effect on the mitogenic effect of LDL. LDL stimulates a number of growth-related genes. These data suggest that lipoproteins may play a critical role in mediating mesangial cell hypertrophy or proliferation, events intimately involved in the development of glomerulosclerosis.

Cell Division↗
PubMed1992

Enumeration of T, B and natural killer peripheral blood cells of patients with multiple sclerosis and controls.

The median percentages of peripheral blood immunoglobulin-positive (Ig+) lymphocytes (8%, n = 46), CD8+ (12%, n = 49) and CD57+ cell numbers (5%, n = 37) of patients suffering from multiple sclerosis (MS) were significantly (p less than 0.05) lower than the values of age- and sex-matched healthy individuals (Ig+ cells: 13%, n = 46; CD8+ cells: 17%, n = 49; CD57+ cells: 9%, n = 37). Comparison of calculations on decreased peripheral blood cell counts and increased brain cell counts in MS patients revealed that sequestration of blood cells into the MS brain is a possible explanation of these findings.

Adult↗
PubMed1992

[Prevention of cardiovascular diseases by intervention in lipid metabolism].

Atherogenesis is a multifactorial event. Experimental, clinical and epidemiological studies, however, have clearly indicated the major role of LDL-cholesterol in the process of cholesterol deposition in the arterial wall. Although most patients with severe hypercholesterolemia suffer from premature coronary heart disease, it is a medical experience, that there are subjects who tolerate hypercholesterolemia and reach high ages without problems of their coronary arteries. Thus, there is much biological variation in the response of the arterial wall to elevated LDL-cholesterol, a fact which emphasizes the need to differentiate between goals and means of primary and the goals and means of secondary prevention of coronary heart disease and between the goals of a population strategy and the goals and means of an individual therapeutic strategy. Today the knowledge about the role of lipids and lipoproteins in atherogenesis is convincing. Epidemiological as well as intervention studies have proven the benefit of an appropriate lipid lowering therapy.

Adult↗
PubMed1992

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin and the human lens. Clinical results of a 3-year follow-up.

Simavastatin (MK-733, Zocor, CAS 79902-63-9), a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was administered for a period of at least 3 years to 21 patients suffering from primary hypercholesterolemia. Significant decreases were noted for plasma cholesterol (30%), low density lipoprotein cholesterol (40%), whereas an increase in plasma high density lipoprotein cholesterol (11%) was observed. The drug therapy was well tolerated and clinical examinations revealed no adverse effects. No development of cataracts or other ocular side effects have been observed during this 3-year follow-up period.

Adult↗
PubMed1992

Risk factor patterns for coronary heart disease in China, Japan and Germany.

The risk factor patterns for coronary heart disease in China, Japan and Germany were studied. 6,025 Germans, 7,580 Japanese and 2,047 Chinese aged 30-59 were investigated following the protocol of the Göttingen Risk, Incidence, and Prevalence Study carried out in West Germany in 1982. It is concluded that in China, the risk factor intervention focuses mainly on smoking and hypertension; smoking also remains the most important risk factor in Japan; while in Germany the major targets are obesity and hyperlipidemia. However, about 38% of the participants from West Germany showed 3 or more risk factors accumulated per person. Thus the multifactorial risk factor reduction might be necessary in Germany.

Adult↗
PubMed1991

Serum Lp(a) concentrations are unaffected by treatment with the HMG-CoA reductase inhibitor Pravastatin: results of a 2-year investigation.

The concentration of lipoprotein (a) in plasma is under stringent genetic control and raised concentrations are strongly linked to coronary heart disease, in particular when low density lipoprotein levels are also increased. We serially monitored serum Lp(a) in 14 hypercholesterolemic patients who were treated with Pravastatin over a period of two years. C-reactive protein levels were also quantified to exclude a possible 'acute-phase' response as a reason for a sudden increase in the Lp(a) concentration. No significant changes were seen in mean Lp(a) levels after 24 months of therapy. Considerable fluctuations of serum Lp(a) levels occurred during the course of treatment. These were in some cases associated with raised C-reactive protein concentrations and might therefore be attributable to an 'acute-phase' response. We conclude that the HMG-CoA reductase inhibitor Pravastatin has no long-lasting effects on Lp(a) levels in hypercholesterolemic patients suffering from coronary heart disease.

Adult↗
PubMed1991

Differences in the risk factor patterns for coronary heart disease in China, Japan, and Germany.

In Asia coronary heart disease mortality is almost 10 fold less frequent than in European countries. These findings attract interest to search for different risk factor patterns. From 1982 to 1985 epidemiologic surveys were carried out in China (n = 2047), Japan (n = 7580) and Germany (n = 6052). Healthy, male subjects, aged 30 to 59 years were enrolled. The prevalence rate of hypertension for the Germans was 20% versus 18% for the Japanese, and 11% for the Chinese. About 69% of Chinese, 55% of Japanese, and 37% of Germans were smokers. About 66% of the Germans were overweight (BMI greater than 25), 17% of the Japanese, and 11% of the Chinese. The highest risk group with cholesterol levels of greater than 300 mg/dl included no Chinese subject, 0.1% of the Japanese, but 5% of the Germans. The lipoprotein profiles among the Japanese and the Chinese collectives typically showed antiatherosclerotic characteristics, whereas most Germans exhibited profiles which support development of atherosclerosis. About 36% of the participants from Germany showed 3 or more risk factors accumulated per person (Japan and China 5%). Multifactorial risk factor reduction for Germany is recommended.

Adult↗
PubMed1991

[Lovastatin efficacy and tolerance in primary hypercholesterolemia. The German Lovastatin Study Group].

In the course of an open multicentre clinical trial 786 patients (512 men, 274 women; mean age 52.4 +/- 11 years) with primary hypercholesterolaemia (total cholesterol 328 +/- 72 mg/dl, triglycerides 174 +/- 87 mg/dl, LDL cholesterol 246 +/- 73 mg/dl, and HDL cholesterol 50 +/- 18 mg/dl) received 20-80 mg lovastatin daily for 12 weeks, after a four-week placebo period. On this regimen the concentration of total cholesterol fell by 27% to 238 +/- 52 mg/dl (P less than 0.001) of triglycerides by 13% to 140 +/- 69 mg/dl (P less than 0.001), that of LDL cholesterol by 36% to 157 +/- 53 mg/dl (P less than 0.001). But HDL cholesterol rose by an average of 12% to 54 +/- 17 mg/dl (P less than 0.001). Lovastatin was tolerated very well by 79% of patients, well by 19%, and poorly by 2%. Mild undesirable side effects of the drug (in particular meteorism, constipation, diarrhoea and nausea) were reported by fewer than 10% of patients. These data indicate that lovastatin is effective and well tolerated also when broadly applied in clinical practice.

Adult↗
PubMed1991

Incidence and mortality rates of myocardial infarction in Chinese workers aged 40-59 in relation to coronary risk factors. Results of a Chinese prospective study (Wuhan Study) in comparison to the Göttingen Risk Incidence and Prevalence Study (GRIPS).

Some 2045 male Chinese industrial workers aged 40-59 years living in the city of Wuhan in the People's Republic of China were examined for coronary risk factors in the year 1983. The investigation included a patient history, clinical examination, and ECG and laboratory tests, with special attention to serum lipids. After 5 years, a follow-up investigation of the study group was carried out. The results were compared to the similarly designed German GRIPS project. In comparison to the German population, significantly lower levels for total-, LDL-, and VLDL-cholesterol, apolipoprotein B, triglycerides, uric acid, body mass index, and diastolic blood pressure were found in China. The percentage of smokers, however, was remarkably higher in China than in the Federal Republic of Germany. During the 5 year observation period in the Chinese sample, four subjects suffered from sudden death and four from nonfatal myocardial infarction; in the German study group three times as many fatal myocardial infarction and cases of sudden death and 7.5 times as many nonfatal myocardial infarctions were recorded. Nonfatal coronary heart disease and peripheral vascular disease were also observed less often in China. The incidence of cerebrovascular diseases was 1.5 times higher in China than in Germany. Whereas in Germany, total-, and LDL-cholesterol values were the major distinguishing parameters between infarction and reference groups, in China these values have thus far had no significant influence on the level of risk. Instead in the Chinese incidence group, significantly higher levels for blood pressure, body mass index, uric acid, and the ratio LDL/HDL-cholesterol were found.

Adult↗
PubMed1991

Clinical relevance of the quantification of apolipoprotein E in cerebrospinal fluid.

Apolipoprotein E was measured in paired sera and cerebrospinal fluid samples from 483 neurological patients. The average apolipoprotein E concentration was 7.5 (+/- 3.1) mg/l in cerebrospinal fluid and 93.5 (+/- 29.7) mg/l in serum. Mean apolipoprotein B concentrations in 88 patients were 0.77 +/- 3.4 mg/l in cerebrospinal fluid and 1.06 +/- 0.31 g/l in serum. The apolipoprotein E concentration in cerebrospinal fluid was much greater than expected for passive diffusion from serum. By contrast to apolipoprotein B, there was no correlation between the apolipoprotein E cerebrospinal fluid/serum concentration quotient and the albumin concentration quotient. This suggests that apolipoprotein E in cerebrospinal fluid, unlike apolipoprotein B, is locally synthesized and that the use of a cerebrospinal fluid/serum concentration quotient is unnecessary. In a control group (n = 64) the mean cerebrospinal fluid apolipoprotein E value (+/- SD) was 5.9 (1.6) mg/l. Elevated cerebrospinal fluid apolipoprotein E concentrations were observed in acute (n = 22, 12.5 +/- 6.2 mg/l) and chronic inflammatory central nervous system diseases (n = 15, 10.4 +/- 2.4 mg/l).

Adult↗
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↗