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D Seidel

Publications and source records attributed to D Seidel.

At least 109 records · Page 6Linked to original sources
PubMed1995

What is the role of lipid lowering therapy in heart-allograft failure?

Hypercholesterolemia is often the cause for the primary heart disease ultimately necessitating heart transplantation (HTx). After transplantation, persisting hypercholesterolemia results in an increased peroxidation of LDL retained by extracellular matrix of the intima. Oxidized LDL accumulates in monocyte derived macrophages, it leads to immobilization of tissue macrophages and provokes the expression of vascular adhesion molecules, growth factors and cytokines. In a prospective open controlled study, the impact of long-term cholesterol reduction by diet in combination with the HMG-CoA-reductase inhibitor Simvastatin on graft vessel disease (GVD) was evaluated. Patients of the control group received only a low fat diet. Simvastatin treatment decreased total and LDL-cholesterol significantly and was not associated with adverse effects. The one year angiographies revealed GVD in 24.1% of the control and 12.1% of the Simvastatin group (Study I). In high risk patients with LDL-cholesterol concentrations above 135 mg/dl, in spite of maximal Simvastatin treatment or plasma fibrinogen concentrations above 400 mg/dl, the heparin mediated extracorporeal low density lipoprotein precipitation (H.E.L.P.)-system was applied. H.E.L.P. was used either for prevention of GVD soon after HTx or for treatment of GVD after development of coronary lesions. Study II proved that the H.E.L.P.-system could significantly lower LDL-cholesterol, Lp(a) and fibrinogen in most high risk patients after HTx, resulting in successful prevention or even treatment of GVD.

Coronary Angiography↗
PubMed1994

Reversible reduction of phospholipid bound arachidonic acid after low density lipoprotein apheresis. Evidence for rapid incorporation of plasmalogen phosphatidylethanolamine into the red blood cell membrane.

In order to evaluate whether acute changes in fatty acids bound to phospholipids in plasma are transmitted into red blood cell membrane (RBCM) phospholipids, molecular species of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were analyzed after reduction of apo B containing lipoproteins through low density lipoprotein (LDL) apheresis in patients with severe hypercholesterolemia. As compared to the control, increases and decreases in molecular species with arachidonic acid (20:4) and with linoleic acid (18:2), respectively, at sn-2 of plasma diacyl-PC were seen in the patients before the apheresis. Directly after the procedure, the sum of species of plasma and RBCM PC plus PE with 20:4 were reduced. Two days after apheresis major species of plasma diacyl-PC reapproached preapheresis values while, in contrast, the composition of plasma alkenylacyl(plasmalogen)-PE was distinctly altered. In plasmalogen-PE of RBCM similar modifications were induced by the apheresis as in the same subgroup in plasma. In vitro experiments using vesicles with plasmalogen-PE labeled at sn-2 with either [14C]20:4 or a fluorescent pyrenedecanoyl residue indicated fast incorporation of the subgroup into the RBCM. In contrast, diacyl-PE was not taken up by the RBCM. In conclusion, apo B containing lipoproteins are partially responsible for the supply of phospholipids with arachidonic acid to RBCM, in particular by means of the fast incorporation of plasmalogen-PE. The transmission of changes induced by apheresis in plasma into those of the RBCM suggest that erythrocytes play an important role in the homeostasis of fatty acids bound to plasma phospholipids in vivo.

Arachidonic Acid↗
PubMed1994

The prognostic value of hypocholesterolemia in hospitalized patients.

Clinical observations show that severe illness often leads to hypocholesterolemia. To verify this finding and to define the relationship between serum cholesterol and a patient's prognosis, a study was conducted in two large hospital populations. Of 24,000 and 61,463 adult patients (populations I and II) an average of 3.8% and 3.6% died in hospital, respectively. The mean serum cholesterol levels of patients who died was significantly lower than that of those who survived (163.6 mg/dl versus 217.8 mg/dl; P < 0.0001). The average cholesterol of surviving patients was similar to that of 6,543 healthy controls. During hospitalization serum cholesterol levels of < or = 100 mg/dl were encountered in 1.2% and 3.6% of patients of populations I and II, respectively. The mortality of these hypocholesterolemic patients was about tenfold higher than average and showed a strong, inverse, linear relationship with serum cholesterol concentrations. Patients whose serum cholesterol level dropped to less than 45 mg/dl did not survive. These data show that in severely ill patients serum cholesterol may decline to very low concentrations, and the prognosis is reflected by the degree of hypocholesterolemia, which thus may serve as a clinically useful prognostic parameter.

Adult↗
PubMed1994

Heparin extracorporeal LDL precipitation (HELP): an effective apheresis procedure for lowering Lp(a) levels.

Heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) is based on the precipitation of apolipoprotein B (apo B) containing lipoproteins with heparin at low pH (4.85). In in vitro experiments we could show that Lp(a) is quantitatively (> 99%) precipitated from plasma by heparin in the pH range 4.6-5.2. The acute changes in Lp(a) after a single HELP-LDL apheresis were investigated in twelve patients with Lp(a) concentrations > 30 mg/dl. A single treatment caused a highly significant decrease (62%) in the concentration of Lp(a), similar to the decrease (60%) observed for LDL-cholesterol. Analysis of the data from ten patients with different apo(a) phenotypes indicated that Lp(a) is eliminated with almost 100% efficiency in the extracorporeal circulation, irrespective of apo(a) phenotype and plasma concentration. The mean rate of recovery of Lp(a) following HELP-LDL apheresis was slightly slower than that of LDL-cholesterol. Plasma Lp(a) concentrations were monitored in seven patients over 2 years. Mean Lp(a) concentrations after 2 years were lower than pre-treatment levels, indicating that repeated elimination of the lipoprotein does not lead to an induction in its synthesis. HELP-LDL apheresis should be particularly suitable for treatment of patients with elevated LDL-cholesterol levels who are also at increased coronary risk because of high Lp(a) concentrations.

Apolipoproteins↗
PubMed1994

The role of lipids in nephrosclerosis and glomerulosclerosis.

Hyperlipidemia and lipoprotein abnormalities are often encountered in patients with nephrotic syndrome or chronic renal disease and also in those undergoing haemodialysis and with renal transplant. Even though the significance of lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis of renal disease in man is unclear, experimental and clinical data indicate a possible damaging effect of a disturbed lipid metabolism on the kidney. In humans, glomerular lipid deposition is observed in genetic diseases such as Fabry's disease, lecithin:cholesterol acyltransferase activity (LCAT) deficiency and arteriohepatic dysplasia, and in diseases with acquired disturbance of lipid metabolism such as nephrotic syndrome and cholestatic liver disease. Studies on animals with lupus nephritis, aminonucleoside nephrosis, reduced renal mass, diabetes mellitus or systemic hypertension have shown that cholesterol can increase the incidence of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different lipoprotein profile to that of man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have given some preliminary insights into the cellular mechanisms of lipid induced glomerular damage. Apo E-containing lipoproteins, which are pathologically elevated in many renal diseases, are avidly taken up by human mesangial cells. These cells seem to play a central role in the initiation of glomerulosclerosis by inducing proliferation and production of excess extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these cells, and increase the synthesis of mitogens and extracellular matrix protein. The pathogenic role of oxidized lipoproteins has not yet been defined. Human mesangial cells do not seem to take up these modified lipoproteins. However, macrophages infiltrate glomeruli and may constitute the stimulus for the generation of minimally modified lipoproteins and their cellular uptake. The data from animal experiments suggest that treatment that corrects hyperlipidemia may have an ameliorative effect on renal function. Thus, there are strong indications that lipoproteins may play a critical role in mediating the development of glomerulosclerosis.

Animals↗
PubMed1994

Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Göttingen Risk Incidence and Prevalence Study (GRIPS).

Based on pathophysiological findings Lp(a) is considered to be a cardiovascular risk factor. The Göttingen Risk Incidence and Prevalence Study (GRIPS) provides the possibility to evaluate this impact of Lp(a) on the basis of a large prospective cohort study. GRIPS included 6002 men, aged 40-59.9 years at baseline. Data of a 5 year follow-up period is now available for > 95% of the study participants. Multivariate logistic regression models for the estimation of MI risk confirm Lp(a) as an important risk factor, ranking fifth behind LDL cholesterol, family history of MI, plasma fibrinogen and HDL cholesterol (inversely related). The GRIPS data strongly support strategies for the identification and treatment of persons at increased MI risk which focus on LDL cholesterol. However, Lp(a) and fibrinogen have to be seriously considered as additional risk factors and should be included in diagnostic panels for the estimation of MI risk.

Cholesterol, LDL↗
PubMed1994

Long-term follow-up of lipid metabolism and rheologic properties after successful pancreas and kidney transplantation.

The long-term effect of pancreatic and kidney transplantation (spkt) on blood viscosity, lipid metabolism and skin microcirculation in insulin-dependent diabetes mellitus (IDDM) was studied because impaired rheological properties of blood may play a role in the development of diabetic micro- and macroangiopathy. 46 IDDM-patients (16 f/30 m; 23 +/- 34 y mean duration of diabetes; 60 +/- 14 mos mean follow up period) underwent spkt (Gr.I: n = 28) or solitary kidney (Gr.II: n = 18) transplantation, and were compared with healthy controls (C). Rheological measurements were performed with Mooney-Ewart rotation-viscosimeter determining whole blood viscosity (WBV), at shear rates 1, 5, 10, 20, 50, 100, 200 sec(-1). Triglycerides, total and HDL-, LDL- and VLDL cholesterol and fibrinogen were measured. Microcirculation was estimated by transcutaneous oxygen tension measurement (tcpO2) and laser speckle method, in the forefoot area. Hemoglobin A1 was normalized only in group I (I: 7.2 +/- 0.2%; II: 8.3 +/- 0.3%; C: < 8%). WBV at low shear (1, 5, 10) was increased in both groups, when compared to healthy controls (I: 12.4 +/- 2; 12.5 +/- 1; 6.8 +/- 0.5 mpas; II: 18.7 +/- 2; 13.4 +/- 15; 9.4 +/- 1 mpas; C: 7.5 +/- 0.5; 6.7 +/- 0.3; 5.4 +/- 0.2 mpas; P < 0.05). Plasma fibrinogen was elevated in both groups compared to normals: (I: 384 +/- 19; II: 448 +/- 20; C: 250 +/- 50 mg/dl; P < 0.05). There was a positive influence of spkt on skin microcirculation: tcpO2/prior tx: I: 44 +/- 3; II: 49 +/- 6 mmHg; post tx: I: 59 +/- 4; II: 42 +/- 3 mmHg. Laser speckle prior tx I: 3.3 +/- 0.3; II: 4.7 +/- 0.2 rel. U.; post tx: 3.8 +/- 0.2; II: 4.3 +/- 0.2 rel. U. Patients with progression of angiopathy showed still higher fibrinogen and shear rates (P < 0.05). There was no significant difference for total HDL-, LDL- and VLDL cholesterol. Despite normalization of glucose metabolism and significant improvement of microcirculation in spkt patients, fibrinogen and the shear rates are increased indicating a persisting "individual" vascular risk. It is suggested that an additional hemorheological approach in the treatment posttrransplant might prevent the progression of vascular complications.

Adult↗
PubMed1994

Characterization and extracorporeal application of a new phosphate-binding agent.

A new phosphate-binding agent which does not cause any severe side effects in vivo was developed by modifying a crosslinked dextran with polynuclear iron(III)oxide-hydroxide. Its particle size ranges from 150 to 300 microns, and the iron content was about 18% by dry weight. The oxidation state of iron was characterized by ESCA and Mössbauer spectroscopy. The maximum phosphate binding capacity of the iron(III)oxide-hydroxide-modified dextran was determined with respect to aqueous phosphate solutions, human serum and whole blood. The effects on whole blood count, haemolysis, protein concentration and enzyme activities were examined. In addition, the influence of phosphate concentration, pH and temperature on the phosphate uptake of the material was determined. The results show that this new adsorbent might provide an alternative to conventional phosphate-binding agents. This paper also describes the first experiments on the therapeutic application of the material in an extracorporeal blood perfusion system for the treatment of hyperphosphataemia during haemodialysis.

Adsorption↗
PubMed1994

[Can hyperlipidemia after heart transplantation be optimally and safely treated?].

"Is there any safe and optimal treatment of hyperlipidemia following heart transplantation?" The problem of hypercholesterolemia following heart transplantation if often underestimated. Up to now there is no concept of therapy allowing an optimal adjustment of lipid parameters. Therapeutical trials using ion exchange resins, derivatives of nicotinic acids and fibrates were not successful due to cyclosporine A interaction, hepatotoxicity and limited efficacy of the applied substances. In a prospective, randomized and controlled trial we investigated the effects of the HMG-CoA-reductase inhibitor simvastatin in heart transplant recipients. The study included 70 patients (simvastatin n = 37, control group n = 33). 8 patients died within the first three months following heart transplantation. Purpose of the study was the adjustment of the LDL-cholesterol values in the simvastatin treated group to < or = 110 mg/dl. Following 24 months of treatment a mean LDL-cholesterol plasma level of 110 mg/dl was obtained. The corresponding mean value of the control group was 150 mg/dl. The difference between both groups was significant (p < 0.001). In the same period the mean HDL-cholesterol values increased by approx. 15% in both groups (no significant difference [p > 0.05]). The ratio of LDL/HDL-cholesterol was significant lower in the simvastatin treated group (2.28) than in the control group (2.94) (p < 0.05). There was no significant difference in Lp(a) values. No adverse side effects were observed within the observation period of 24 months, particularly no increase in the frequency of rejection episodes. Summarizing the above, we recommend low-dose simvastatin therapy as a safe and optimal treatment of hypercholesterolemia following heart transplantation.

Adult↗
PubMed1994

Gastric antral vascular ectasia: a case report of a 10 year follow-up with special consideration of histopathological aspects.

The diagnosis of gastric antral vascular ectasia (GAVE) was made in a 67 year old patient with a ten year course of the disease, which was characterized by non-ulcerous dyspeptic symptoms in its early phase. The patient was treated successfully by antrectomy. The morphologic findings in the biopsy material ten to eight years before the operation corresponded with those of gastritis type C. The highly characteristic morphologic findings of sinusoidal capillary ectasia and multiple vascular thromboses appeared only in later biopsies taken during the work-up for iron deficiency anemia. The cause of the mucosal alterations was an acquired submucosal vascular anomaly (malformation).

Aged↗
PubMed1993

LDL-apheresis: clinical experience and indications in the treatment of severe hypercholesterolemia.

LDL-cholesterol is the leading risk factor which influences the clinical outcome of patients with preexisting coronary heart disease. Clinical trials show that 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 1 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. We now report about our long-term clinical experience with the H.E.L.P. system in treating patients with different lipoprotein disorders: (1) Homozygous form of familial hypercholesterolemia; (2) CHD patients with familial and non-familial hypercholesterolemia; (3) CHD patients with very high concentrations of lipoprotein(a); and (4) Hypercholesterolemic patients after heart transplantation. Based on present experience guidelines for secondary prevention of coronary heart disease indications for the H.E.L.P.--LDL-apheresis treatment are discussed.

Adolescent↗
PubMed1993

Role of lipoproteins in progressive renal disease.

Renal diseases are often associated with hyperlipoproteinemia and dyslipoproteinemia. Total serum cholesterol and triglycerides are increased in nephrotic syndrome regardless of etiology. Approximately 40 to 50% of patients with renal insufficiency requiring hemodialysis show hypertriglyceridemia and dyslipoproteinemia. During chronic hemodialysis, high doses of unfractionated heparin deplete post-heparin lipolytic activity and aggravate dyslipoproteinemia. Hypercholestrolemia and hyperlipoproteinemia are often encountered in patients taking glucocorticoids and cyclosporin A after renal transplantation. Observations in experimental animals and in patients with genetically determined and acquired hyperlipidemias suggest that lipids can damage the kidney and lead to glomerulosclerosis. In vitro cell-culture studies of human glomerular cells have been useful in providing information on lipid-induced glomerular damage. Thus, there are strong indications that lipoproteins may play a critical role in the development of mesangial cell damage and progressive renal disease. Therapeutic measures that reduce and correct dyslipoproteinemia in renal disease may have long-term beneficial effects on the amelioration of renal disease.

Humans↗
PubMed1993

No evidence for feedback inhibition of hepatic apolipoprotein B (apo B) production after extracorporeal low density lipoprotein precipitation as determined by [1-13C]leucine infusion in normal volunteers.

To determine the impact of an acute reduction of the circulating mass of apolipoprotein B (apo B) on apo B metabolism we studied six healthy male volunteers before (day 0), 1 day after (day 2), and 7 days after (day 8) an LDL apheresis treatment which reduced apo B mass by 59%. Appearance of newly synthesized apo B in plasma VLDL and LDL was studied using a primed-constant infusion of [1-13C]-leucine. VLDL apo B pool size and fractional VLDL apo B production rate calculated using a one-compartment model were similar on all 3 study days. Absolute VLDL apo B production was not statistically different throughout the study (19.7 +/- 12.3, 19.5 +/- 7.5, 29.1 +/- 17.7 mg kg-1 day-1). LDL apo B fractional production rate was increased on day 2 (0.38 +/- 0.17, 0.68 +/- 0.08, 0.37 +/- 0.06 pools day-1 on days 0, 2, and 8; P < 0.01). Absolute LDL apo B production, however, remained constant throughout the study (10.8 +/- 3.3, 11.0 +/- 1.9, 10.8 +/- 3.1 mg kg-1 day-1). We conclude that in healthy male volunteers acute reduction of the circulating apo B mass by LDL apheresis does not affect apo B metabolism significantly.

Adult↗
PubMed1993

A loading-dose strategy for converting from oral to depot haloperidol.

OBJECTIVE: The author's aim was to evaluate the safety and efficacy of a loading-dose regimen for initiating use of a depot medication, haloperidol decanoate, with patients who had been maintained on oral haloperidol. Patients were given a loading dose of about 20 times their oral maintenance dose in divided injections during the first two weeks of conversion to depot medication. The dose of haloperidol decanoate was gradually reduced, dropping to about ten times the oral dose in the third and fourth months. No supplemental oral medication was used. METHODS: Haloperidol decanoate was initiated using the loading-dose regimen in 16 chronically ill patients. Lower initial doses of haloperidol decanoate were used in two other groups of patients, one that received supplemental oral haloperidol and one that did not. Plasma levels of haloperidol, severity of illness, and side effects were monitored from baseline to 56 days after the beginning of depot therapy. RESULTS: Patients who received the loading-dose regimen showed statistically significant clinical improvement and reduced side effects over baseline by the 28th day. The second group of patients also maintained therapeutic response but improved no further. The third group relapsed during the first month and were returned to a regimen of oral haloperidol by the second month. CONCLUSIONS: A loading-dose regimen for initiating treatment with haloperidol decanoate is safe and effective and can be useful in a clinical setting.

Administration, Oral↗