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Biomedical subjects

E Riedel

Publications and source records attributed to E Riedel.

At least 55 records · Page 3Linked to original sources

Changed purine nucleotide concentrations and enzyme activities in erythrocytes of haemodialysis patients undergoing erythropoietin therapy.

Therapy of renal anaemia in haemodialysis patients with chronic renal failure by application of recombinant human erythropoietin leads to an increase of the haematocrit. Rejuvenation of the erythrocyte population results in a decrease of the median density (D50), an increase of cell age-dependent enzyme activities, such as aspartate aminotransferase, and elevated concentrations of purine nucleotides in the erythrocytes. After density gradient separation of erythrocyte populations into cell age-dependent fractions, the concentrations of adenosine-5'-triphosphate, guanosine-5'-triphosphate and guanosine-5'-diphosphate were be found to be elevated by 25-100% in all cell fractions from haemodialysis patients, compared with a healthy control group. Therapy of haemodialysis patients with recombinant human erythropoietin leads to further increase (65%) of ATP in the younger (low density) cells, but not in the older (high density) cells. The elevated concentrations of ATP and total adenine nucleotides during recombinant human erythropoietin therapy possibly result in improved deformability of erythrocytes. The data point to an enhancement of the proportion of younger erythrocytes, but not to an improvement of the reduced life span of erythrocytes of haemodialysis patients during therapy with recombinant human erythropoietin.

Adenosine Diphosphate↗

Comparative pharmacokinetics of chlorambucil and prednimustine after oral administration.

The pharmacokinetics of chlorambucil, phenylacetic acid mustard (the beta-oxidation product of chlorambucil), and prednisolone were investigated in a cross-over study after oral administration of chlorambucil (30 mg) + prednisolone (50 mg) versus prednimustine (300 mg), the ester of chlorambucil and prednisolone. Intact prednimustine could not be detected in plasma at any time. After administration of prednimustine, the plasma concentration-time curves of chlorambucil, phenylacetic acid mustard, and prednisolone showed a retarded profile compared to the administration of the single components. The mean bioavailability was 14% for chlorambucil, 21% for phenylacetic acid mustard, and 22% for prednisolone, when given as prednimustine, compared to the administration of free compounds in stoichiometrically equivalent doses. When given in the oral dosages mentioned above, the average dose-intensity was 62% for chlorambucil, 95% for phenylacetic acid mustard, and 72% for prednisolone, indicating sufficient therapeutic concentrations of the detectable agents.

Administration, Oral↗

Preparation of nucleoside-LDL-conjugates for the study of cell-selective internalization: stability characteristics and receptor affinity.

Antiviral therapy of human immunodeficiency virus (HIV) infection is currently based on inhibition of reverse transcriptase by dideoxynucleosides, such as azidothymidine. Because of widespread toxicity it is reasonable to selectively target these drugs to infected cells. This may be accomplished utilizing drug-LDL conjugates, which are internalized via cell specific receptor pathways. With respect to HIV infection, scavenger receptors of the macrophage system seems to offer a hopeful perspective. This pathway requires chemical modification of surface polarity of the LDL. Cell experiments were conducted in HepG2 hepatocytes, which express apolipoprotein B receptors, and in P388 macrophages, which express scavenger receptors. LDL particles to be conjugated were isolated from blood donor plasma and from LDL-apheresis waste material. Non-covalent LDL conjugation with amphiphilic nucleoside derivatives produced only an unspecific nucleoside transfer to cell membranes, due to instability of the LDL conjugates. An experimental method (coincubation test) was developed to identify those conjugates that are stable in the presence of other lipophilic compartments. Covalent coupling of nucleosides to the apolipoprotein B moiety of LDL particles resulted in stable conjugates. As a consequence, the surface charge became negative, and the LDL displayed scavenger receptor affinity rather than apolipoprotein B receptor affinity. Selective targeting of nucleosides to macrophages can be accomplished by covalent coupling to LDL.

Animals↗

Erythropoiesis and erythrocyte age distribution in hemodialysis patients undergoing erythropoietin therapy.

Renal anemia is caused in part by a reduced life span of red blood cells (RBCs) and by reduced erythropoietin biosynthesis in the damaged kidney. The RBC age can be determined by density gradient centrifugation and estimation of cell-age-dependent enzyme activities, as aspartate aminotransferase. The RBC age distribution influences the median density (D50) of RBCs and the blood rheology in coherence with the hematocrit. In our study, the median density was determined by Percoll density gradient centrifugation in 18 healthy subjects (D50 = 1.0674 +/- 0.0016 g/ml) and in 14 hemodialysis patients (D50 = 1.0674 +/- 0.0016 g/ml in the course of recombinant human erythropoietin (rhEPO) therapy. During the first 4 weeks of therapy, a strong rejuvenation of RBCs was observed whereby the D50 reached a minimum after 2 weeks (D50 = 1.0655 +/- 0.0022 g/ml; p less than 0.05 vs. value before therapy) and a steady state after 4 weeks (D50 = 1.0658 +/- 0.0013 g/ml; p less than 0.1 vs. value before therapy). In 5 of the patients with elevated plasma parathyroid hormone (i-PTH) concentrations greater than 10 pmol/l, a significantly (p less than 0.05) reduced amount of younger RBCs (D50 = 1.0675 +/- 0.0016 g/ml) was observed in the first 2 weeks of rhEPO therapy as compared to patients with i-PTH less than 10 pmol/l (D50 = 1.0677 +/- 0.0019 g/ml). Thus, erythropoiesis in the early phase of rhEPO therapy is strongly influenced by elevated plasma i-PTH concentrations. Therefore, a gradual increase in rhEPO doses is preferable before therapy at elevated doses with an uncontrolled increase in RBC amount.

Adult↗

Red blood cell density distribution in uremic patients on acetate and bicarbonate hemodialysis.

Renal anemia is the result of reduced erythropoietin (EPO) biosynthesis in the diseased kidney and also in part the result of a reduced life span of red blood cells (RBCs). An increase in density and a decrease in enzyme equipment (aspartate aminotransferase; GOT) of RBCs reflect cell age. In the following study, the density distribution (median density D50; determined by Percoll density gradients) and GOT activities of RBCs were measured in patients on acetate (HDA; n = 15) and bicarbonate (HDB; n = 51) hemodialysis. Hemoglobin (Hb) concentrations were: in the HDB group, 9.1 +/- 3.4 g/dl; in the HDA group, 6.2 +/- 1.2 g/dl, and, in a control (C) group of healthy persons, 14.0 +/- 1.5 g/dl. 14 HDB patients with severe anemia received EPO therapy during 1 year. D50 were found as follows: group C, 1.0674 +/- 0.0016 g/ml; HDB, 1.0674 +/- 0.0015 g/ml, and HDA, 1.0660 +/- 0.0012 g/ml (HDA vs. group C: p less than 0.05; HDA vs. HDB: p less than 0.05. D50 were elevated in the subgroups of HDA and HDB patients with severe anemia (Hb less than 8 g/dl). During activated erythropoiesis by EPO therapy, D50 decreased from 1.06739 +/- 0.0015 to 1.0656 +/- 0.0014 g/ml. The GOT activities in RBCs demonstrated a rejuvenation of the RBC population in the HDB group (6.4 +/- 2.5 U/g Hb) and HDA group (5.9 +/- 3.1 U/g Hb) compared to group C (3.9 +/- 1.3 U/g Hb).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Functional characteristics of LDL particles derived from various LDL-apheresis techniques regarding LDL-drug-complex preparation.

Low density lipoproteins (LDL) have the potential to serve as cell specific drug carriers. The LDL may be derived in large quantities from LDL-apheresis procedures. Therefore, LDL particles isolated from the waste of three types of LDL-apheresis were investigated concerning their functional integrity in cell transport tests. LDL particles obtained from dextran sulfate-apheresis (DSA) and heparin extracorporeal lipoprotein precipitation (HELP)-LDL-apheresis are capable of specific internalization into HepG2 cells via the apoB receptor pathway. DSA-LDL-apoB appears to be split into two fragments as judged by SDS gel-polyacrylamide gel electrophoresis without changing transport behavior. Membrane differential filtration (MDF)- and HELP-derived LDL particles showed parallel transport behavior and electrophoretic mobility. Acetylated LDL particles obtained from MDF-LDL-apheresis and from blood donation plasma were transported into P388-macrophages via the scavenger receptor pathway. The results confirm the use of LDL particles from LDL-apheresis as substrates for transformation into drug carriers.

Animals↗

Changes in the concentrations of hydroxyproline, glycine and serine in the plasma of haemodialysis patients undergoing erythropoietin therapy.

The concentrations of proline, hydroxyproline, glycine and serine were determined in the plasma of 39 haemodialysis patients and 18 healthy subjects, using liquid chromatography with fluorescence detection. Plasma concentrations of the N-terminal immunoreactive parathyrin were also measured. In haemodialysis patients, the plasma concentrations of glycine (p less than 0.01), hydroxyproline (p less than 0.05) and proline (p less than 0.10) were significantly increased, whereas the serine concentrations (p less than 0.01) were decreased, compared with those of the healthy controls. Haemodialysis patients showed greatly elevated plasma N-terminal immunoreactive parathyrin values (greater than 30 pmol/l), which showed a significant correlation with the hydroxyproline values (r = 0.79). Fourteen haemodialysis patients received erythropoietin therapy. In these patients, changes in the concentrations of plasma amino acids were observed up to one year after the beginning of therapy. In the course of the erythropoietin therapy, the plasma concentrations of glycine (p less than 0.05) and hydroxyproline (p less than 0.10) of the haemodialysis patients decreased, whereas the concentration of serine increased (p less than 0.05) to approximately normal values. The results indicate that erythropoietin therapy leads to a normalization of amino acid metabolism.

Adult↗

[The hemodynamics of the lung circulation of minipigs after experimentally-caused Sedlarik's pulmonary embolism. II. Modification of the hemodynamics of the heart and circulation by thoracotomy].

The systolic, diastolic, and the mean arterial systemic blood pressure decreased after thoracotomy (by -12%). The systolic, diastolic, and the mean pulmonary arterial pressure showed an immediate decrease (by 25%). The central venous pressure was not changed. The cardiac output (HMV) and the stroke volume could not be measured before the thoracotomy. However, the HMV (+17%), the HMV-index (+30%), and the stroke volume (+60%) increased from the 10th to the 30th min after the thoracotomy. The heart rate decreased continuously (by -19%). The maximum rate of pressure rise (dp/dtmax) increased primarily insignificantly and decreased afterwards (by -10%). The quotient dp/dt/p decreased immediately (by -10%). All measures were carried out until the 30th min after thoracotomy.

Animals↗

[The hemodynamics of the lung circulation of minipigs after experimentally-caused Sedlarik's pulmonary embolism. III. Sedlarik's embolization of the lung circulation by electrically-activated blood].

Pulmonary embolisms of different clinical degree of severity can be produced by means of the pulmonary embolism model according to Sedlarik by application of electrically activated blood as a thrombogenic substance. An unambiguous influence of the size and the consistency of the thrombus exists concerning the severity of the hemodynamic changes. However, the hemodynamics seems to adapt to the changed conditions of the circulation, because a tendency to normalization was observed in short-term experiments. The morphologic changes after embolisation are more typical for the severity of the clinical picture in this acute phase than the hemodynamics. A testing of the animal model in long-term experiments seem to be ingenious for that reason.

Animals↗

Correction of amino acid metabolism by recombinant human erythropoietin therapy in hemodialysis patients.

We assessed the effect of correction of anemia with recombinant human erythropoietin (rhEPO) on plasma amino acid levels in maintenance hemodialysis patients. The plasma amino acid pattern was estimated by high performance liquid chromatography in 18 healthy persons and 14 hemodialysis patients before and up to 12 weeks after rhEPO therapy. There was a correction of the plasma serine values (67 +/- 16 to 87 +/- 22; P less than 0.05) and a corresponding decrease in the serine precursors, glycine (317 +/- 113 to 228 +/- 56; P less than 0.05) and hydroxyproline (26 +/- 21 to 15 +/- 13; P less than 0.10). The low plasma branched-chain amino acids, valine (137 +/- 33 to 154 +/- 50; P less than 0.10) and leucine (72 +/- 22 to 80 +/- 27; P less than 0.20), also were corrected. The elevated values of ornithine (78 +/- 16 to 62 +/- 19; P less than 0.1) and arginine (94 +/- 14 to 72 +/- 14; P less than 0.1) fell. The diminished glutamine values (470 +/- 125 to 563 +/- 115; P less than 0.1) and the decreased tyrosine/phenylalanine ratio (0.78 +/- 0.17 to 0.98 +/- 0.21; P less than 0.05) rose. Thus, the administration of rhEPO not only affects erythropoiesis, but also corrects the plasma amino acid pattern towards normal.

Adult↗

Clinico-neurophysiological correlations in chronic alcoholic Korsakoff patients.

A group of 29 patients with chronic alcoholic KORSAKOFF syndrome (KS) showed a cumulative increase in the interpeak latencies (IPL)I-II to I-VII of the brainstem auditory evoked potentials (BAEP), highest significance with IPL I-VI (p = 7.27 X 10(-6). The KORSAKOFF core group showed higher multiple correlation coefficients R for the IPL than the KS with additional deficiencies of cerebral performance. The BAEP should be used for recording subclinical patterns of brainstem lesions in risk patients with chronic alcoholism.

Alcohol Amnestic Disorder↗

[Clinico-functional studies in patients with bird fancier's lung].

Bird fancier's lung is a typical manifestation of extrinsic allergic alveolitis. In 107 cases with etiologically and histologically verified diagnosis tests of pulmonary function and hemodynamics were performed at admission to hospital and after 2-3 years of allergen abstinence and therapy. Acute forms of disease show distinct functional improvement, while chronic forms lead to increasing impairment.

Alveolitis, Extrinsic Allergic↗

[Diagnostic score in heart sarcoidosis].

Basis of the score is the empirical valuation of clinical and cardiac functional parameters. The degree of probability shall enable the applier either to temporize and conclude therapeutic steps or considering the diagnostic stage to add additional examinations in order to confirm the supposition. The importance of this diagnostic and therapeutic management rests on the vital danger to patients with heart sarcoidosis. We arranged the score according to the clinical significance intentionally applying strict standards mainly with regard to the differential diagnosis of the coronary heart disease. Due to our results the myocardial biopsy seems to be unnecessary.

Adult↗

[Acoustic evoked brain stem potentials in chronic alcoholic Korsakoff syndrome].

29 patients with Korsakoff syndrome (KS) were examined by means of brainstem auditory evoked potentials. The interpeak-latencies were delayed cumulative with the most accentuation of IPL I-VI. BAEP are suitable for subdividing of KS. It is suggested that BAEP shall observed in alcoholics for detection of norm-deviations.

Alcohol Amnestic Disorder↗

Experimental pulmonary embolism with electrically activated autologous blood.

Pulmonary thromboembolism is one of the most frequent causes of death in our days. Notwithstanding the great efforts made in clinical and experimental medicine there has been no success as yet in filling the existing gaps in the understanding of pathophysiology of this disease. The blood electrically activated in vitro by direct current reacts like an endogenic thrombogenic substance. On the condition that such a substance is injected into the inferior vena cava, the clot is introduced into the pulmonary circulation and gives rise to pulmonary thromboembolism of a varying degree, each depending on the electrically activated blood injected. In the animal experiment it has thus become feasible, under standardized and reproducible conditions, to produce severe thromboembolism or chronic microembolism with subsequent hypertrophy of the right ventricle. The object of this contribution is a demonstration of a new, easy, and effective method for the induction of pulmonary embolism, which can be treated by thrombolysis.

Animals↗