Search PubMed⌕ Search

Biomedical subjects

H Wieland

Publications and source records attributed to H Wieland.

At least 109 records · Page 6Linked to original sources

Effect of simvastatin on qualitative and quantitative changes of lipoprotein metabolism in CAPD patients.

The efficacy of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 12 patients treated with continuous ambulatory peritoneal dialysis (CAPD), displaying hypercholesterolemia and moderate hypertriglyceridemia. After a 4-week placebo period, simvastatin was administered in increasing doses over a period of 3 months (1st month 10 mg; 2nd month 20 mg and 3rd month 40 mg day-1). Simvastatin reduced total serum cholesterol (300.0 +/- 15.5 vs. 193.0 +/- 8.0; -35%), LDL cholesterol (203.8 +/- 13.0 vs. 104.7 +/- 6.0; -48.0%) as well as apolipoprotein B (132.3 +/- 6.6 vs. 77.8 +/- 2.7 mg/dl; -40%). Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.55 +/- 0.016 vs. 0.64 +/- 0.027). Another remarkable effect was the reduction of cholesterol concentration in VLDL (47.8 +/- 5.6 vs. 30.4 +/- 5.2; -35%). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.57 +/- 0.3 vs. 4.28 +/- 0.29), indicating VLDL formation poor in cholesterol and rich in triglycerides. However, HDL cholesterol increased significantly from 48.6 +/- 4.4 to 57.9 +/- 5.3 mg/dl (23%). Lipoprotein(a) levels were increased as compared to controls (420 +/- 73 vs. 145 +/- 26 U/l), but were not influenced significantly by simvastatin treatment (539 +/- 99 U/l, 3rd month). No evidence for notable clinical side effects and laboratory abnormalities were reported. Measurement of simvastatin plasma levels 12 h after drug administration (single dose 40 mg) showed no detectable plasma values. At present, it appears that CAPD patients with high serum cholesterol are good candidates for the treatment with HMG-CoA reductase inhibitors.

Adult↗

Effect of magnesium pyridoxal 5-phosphate glutamate on the hamster cardiomyopathy.

30-day-old polymyopathic hamsters (strain BIO 82.62) were orally treated with either magnesium pyridoxal 5-phosphate glutamate 100 mg/kg, equimolar amounts of magnesium alone (MgCl2 55 mg/kg), or water b.i.d. for 30 days, or sacrificed before treatment. 60-day-old healthy hamsters (strain CLAC) served as controls. Magnesium pyridoxal 5-phosphate glutamate lowered the myocardial calcium content (42.8 +/- 13.1 mmol/kg dry weight) as compared to MgCl2 (70.3 +/- 11.9 mmol/kg dry weight) and water (72.7 +/- 13.6 mmol/kg dry weight). The serum and tissue lipid pattern did not differ between BIO 82.62 and normal hamsters except high serum cholesterol and triglyceride levels in 30-day-old BIO 82.62 hamsters. Myocardial necroses were influenced by neither magnesium pyridoxal 5-phosphate glutamate nor MgCl2. Cytochemical investigation of the ultrastructural calcium localization in the aorta revealed less calcium precipitates with magenesium pyridoxal 5-phosphate glutamate in media myocytes. It is concluded that magnesium pyridoxal 5-phosphate glutamate exerts a calcium antagonistic effect in the cardiomyopathy of the Syrian hamster which is related neither to the magnesium content of magnesium pyridoxal 5-phosphate glutamate nor to its lipid lowering activity.

Animals↗

Practical aspects of monitoring cardiac drugs in the blood.

Various factors known to affect digoxin blood values are discussed in the present review. A reduction as well as an increase in digoxin levels may be due to the method employed, to errors in the preanalytical phase, to peculiarities of the patient, to diseases or to the administration of drugs. Increased digoxin concentrations above the therapeutic range are much more common than manifestations of digoxin intoxication. However, geriatric patients are specially sensitive to intoxication. Attention has to be paid to digoxin-like immunoreactive factors (DLIF) being synthesized under certain physiologic and pathophysiologic conditions which cause falsely elevated values in digoxin-immunoassays. The determination of digoxin levels is indicated in suspected intoxication or hypersensitivity to digoxin, in patients with pacemakers or those receiving certain drugs, in old people and in patients suffering from any concomitant disease. The time of blood collection has to be carefully controlled in order to determine digoxin concentrations of diagnostic value, the physical activity of the patient being a main influencing factor.

Digitoxin↗

Results of the multicenter evaluation of a homogeneous immunoassay for digitoxin based on the cloned enzyme donor immunoassay technology.

We evaluated a CEDIA assay for the determination of digitoxin in serum on random access analyzers. The multicenter evaluation included studies on the analytical range, calibration stability and reproducibility of the new assay. Moreover, recovery in controls, transferability of results obtained in different laboratories, comparability with routine methods, and the effect of various interfering factors have been analyzed. Summarized the analytical performance was comparable to that of routine methods. The CEDIA Digitoxin assay represents an attractive alternative to established digitoxin immunoassays because it can be performed on random access analyzers, thus permitting the simultaneous determination of digitoxin and other serum analytes without sample splitting.

Digitoxin↗

Fish oil treatment and apolipoprotein(a).

Two recent reports showed a lowering of elevated lipoprotein(a) levels upon treatment with fish oil. The aim of this paper was to confirm this finding and to establish a dose-effect relationship. A double blind, placebo controlled cross-over study was carried out in 48 subjects with apolipoprotein(a) ("Apo(a)") values between 34 and 1062 U/l (median 387 U/l). The subjects were divided into 3 groups receiving 3.5, 7.1 and 10.6 g omega-3 fatty acids/day during 28 days. Parameters measured were blood levels of eicosapentaenoic acid ("EPA"), Apo(a) and fasting blood lipids. EPA levels rose in the three dosage groups by factors 7, 9 and 14, respectively, if compared to values upon placebo. Triglycerides were significantly lowered in a dose depending manner. Apo(a), however, was not changed. This held true for different baseline Apo(a) values and different fish oil dosages. It is concluded that fish oil treatment during 4 weeks cannot lower elevated Apo(a) levels.

Adult↗

Cloning, pharmacological characteristics and expression pattern of the rat GABAA receptor alpha 4 subunit.

A cDNA of rat brain encoding the GABAA receptor alpha 4 subunit has been cloned. Recombinant receptors composed of alpha 4, beta 2 and gamma 2 subunit bind with high affinity the GABA agonist [3H]muscimol and the benzodiazepine 'alcohol antagonist' [3H]Ro 15-4513, but fail to bind benzodiazepine agonists. The alpha 4 subunit is expressed mainly in the thalamus, as assessed by in situ hybridization histochemistry, and may participate in a major population of thalamic GABAA receptors. The alpha 4 mRNA is found at lower levels in cortex and caudate putamen, and is rare in cerebellum.

Affinity Labels↗

Effects of HMG-CoA reductase inhibitors in hypercholesterolemic patients on hemodialysis.

The efficacy of lovastatin and simvastatin, competitive inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 40 hemodialysis (HD) patients displaying hypercholesterolemia and moderate hypertriglyceridemia (selection of 40 patients required screening of 700 hemodialysis patients). After a four-week placebo period, lovastatin or simvastatin was administered to two groups of 20 patients in increasing doses over a period of three months. Thirty-six patients completed the study. Lovastatin (1st month 20 mg; 2nd and 3rd months 40 mg day-1) and simvastatin (1st month 10 mg, 2nd month 20 mg and 3rd month 40 mg day-1) reduced total serum cholesterol from 280.3 +/- 9.4 to 213.0 +/- 6.7 (-24%) and 295.0 +/- 12.2 to 202.3 +/- 8.9 mg/dl (-31.4%), LDL cholesterol from 161.9 +/- 10.7 to 112.1 +/- 7.9 (-30.8%) and 181.8 +/- 14.7 to 107.4 +/- 8.1 mg/dl (-40.9%), as well as apolipoprotein B (apo B) from 116.0 +/- 6.6 to 83.3 +/- 3.7 (-28.2%) and 134.4 +/- 8.2 to 84.1 +/- 5.3 mg/dl (-37.4%), respectively. Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.63 +/- 0.02 vs. 0.71 +/- 0.05 and 0.63 +/- 0.02 vs. 0.66 +/- 0.02, respectively). Another remarkable effect was the reduction of cholesterol concentration in VLDL (72.4 +/- 8.9 vs. 47.3 +/- 6.8 [lovastatin] and 78.3 +/- 11.1 vs. 50.7 +/- 8.8 mg/dl [simvastatin], respectively). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.2 +/- 0.2 vs. 3.8 +/- 0.3 and 3.2 +/- 0.2 vs. 4.0 +/- 0.2, respectively), indicating VLDL formation poor in cholesterol and rich in triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biocompatibility of four plasmapheresis membranes in patients treated for hypercholesterolemia.

Membrane plasma separation uses artificial polymers which might interact with blood components during treatment. In 7 patients treated for familial hypercholesterolemia with heparin-induced extracorporeal LDL precipitation (HELP), we studied 4 different synthetic plasma separation materials. The effect of membranes made from polyethylene, polymethylmethacrylate (PMMA), polypropylene and polysulfone on complement activation (C3a), granulocyte elastase release and granulocyte count were measured repeatedly during the treatment. Polyethylene and PMMA induced high levels of plasma elastase and marked granulocytopenia after 60 min of treatment, much later than during hemodialysis, where granulocyte nadir is known to occur already after 15 min. Polysulfone and polypropylene did not change granulocyte counts and caused only modest levels of elastase during plasmapheresis. Complement activation was present in all 4 membranes but with polyethylene, very high concentrations of C3a were detected. These data indicate that irritation of immune system components as granulocytes or the complement system do occur during plasmapheresis to different degrees depending on the membrane material used. Reinfusion of plasma after processing increases the amount of plasmatic activation products infused into the patient. This was the case, although the plasma processing procedure itself did not add activation products to the plasma. Activation patterns during plasma separation differ from those known to occur during hemodialysis despite use of the same polymer. Immunocompromised patients treated with plasmapheresis may react differently than these otherwise healthy subjects with familial hypercholesterolemia.

Biocompatible Materials↗

A case of the Hb Regina (beta 96 (FG3) Leu----Val) in a German male associated with high oxygen affinity and erythrocytosis.

Hb Regina was identified in a 58-year-old German male and 2 of his 3 children. All affected subjects presented moderate erythrocytosis and the whole blood exhibited increased oxygen affinity (P50:17.5 mm Hg). This hemoglobinopathy was undetectable with the conventional electrophoretic methods. It was, however, separated and quantified by cation-exchange and reverse-phase high-performance liquid chromatography. Hb Regina accounted for 30-35% of the total Hb. No significant clinical symptoms were found to be related to this hemoglobinopathy. This is the first known instance in Germany, and so far the second case reported.

2,3-Diphosphoglycerate↗

[An apparatus for olfactory isolation of small mammals for the study of chemocommunication].

Olfactory isolation of individual experimental and control animals seems to be necessary to investigate the role of chemosignals in the biology of small rodents. Each cage was isolated in a polyethylene bag and applied with purified air drawn through wash bottles containing concentrated sulphuric acid. Sulphuric acid aerosols were bound with saturated calcium chloride. Calcium chloride served also to humidify the air. Possible improvements to the apparatus are discussed.

Animal Communication↗

Sequelae after infection with Trichinella spiralis: a prospective cohort study.

It is still a matter of debate whether or not infection with Trichinella spiralis is followed by long lasting sequelae. A common source epidemic of trichinosis which occurred in Bitburg, FRG, in October 1982 gave us the opportunity of performing a controlled cohort study (171 patients and 51 controls). 145 patients and 44 controls completed the 3 year follow-up. Complaints persisted in 36% of patients aged less than 30 years and in 100% of patients aged greater than 50 years. Complaints in order of frequency were: muscular complaints 84%, ocular complaints 63%, cardiac complaints 48%, cephalgia 43%, neurological complaints 35%, gastrointestinal complaints 18%, m fatigue and weakness 18%, oedema 12% and fever less than 1%. IgG antibodies to T. spiralis were still present in all but 5 patients 3 years after infection. IgM antibodies were either low or absent. In our patients the frequency and pattern of complaints and the correlation to the specific antibody response provide evidence that trichinosis causes long-lasting disease. Yet, from our data we were unable to draw conclusions as to the causative pathophysiological mechanisms.

Adolescent↗

Beclobrate:pharmacodynamic properties and therapeutic use in hyperlipidemia.

Beclobrat is a new fibric acid derivative with potent cholesterol- and triglyceride-lowering effects. Pharmacodynamic and pharmacokinetic investigations suggest that once-daily administration in a dosage of 100 mg is admissible. In comparison with other lipid-lowering drugs such as dose, even when calculated on a molar basis, is as effective as 300 mg fenofibrate, 600 mg bezafibrate or 900 mg gemfibrozil. The effectiveness of the drug has been investigated in a variety of studies including patients with hyperlipidemia types IIa, IIb and IV and patients suffering from secondary hyperlipidemia attributable to diabetes mellitus, liver disease, end-stage renal failure requiring hemodialysis, and kidney transplantation. According to the type of hyperlipidemia studied, the mean reduction of LDL-cholesterol ranges from -10% to -28% and that of triglycerides from -20% to -58%. Mean serum HDL-cholesterol increase has been reported to be 8.5-23.9%. In general, side-effects of beclobrate therapy are comparable with those of other fibric acid derivatives, but have to be investigated carefully in a greater number of patients. Advantages in clinical use are administration of a small capsule in a single daily dose. This has been shown to increase patient compliance and is especially useful for treatment of hyperlipidemia in those patients requiring antihyperlipidemic combination therapy or additional medication for further diseases.

Benzhydryl Compounds↗

Rapid apolipoprotein E phenotyping by immunofixation in agarose.

Conventional determination of apolipoprotein E isomorphs comprises ultracentrifugation of 1-5 ml serum, delipidation of very low density lipoproteins (VLDL), and isoelectric focusing (IEF) in polyacrylamide gels. In order to reduce the sample volume and to avoid nonspecific protein bands, immunoblotting was proposed. Now we describe a methodological variant that uses 25 microliters serum, replaces ultracentrifugation by precipitation of apoE-containing lipoproteins with polyethylene glycol, and delipidation by dissolution in detergent. IEF is carried out in agarose. This allows specific immunofixation of apoE-containing bands with 10 microliters antiserum per sample. This method yields apoE patterns that are specific and well resolved. Also, it offers considerable savings of time and equipment involved.

Apolipoproteins E↗

Altered concentrations, patterns and distribution in lipoproteins of serum gangliosides in liver diseases of different etiologies.

Concentrations, patterns and distribution in different lipoprotein classes of human serum gangliosides were investigated in acute and chronic liver diseases of different etiologies. The total concentrations of gangliosides were moderately elevated in sera of patients with cirrhosis and acute B or NANB virus hepatitis, but almost 3-fold in those with severe cholestasis. Up to three unknown gangliosides appeared in the sera of six out of nine patients with alcoholic cirrhosis. They accounted for 11-27% of total serum gangliosides. In acute viral hepatitis very small amounts of these gangliosides were inconsistently detected. In severe cholestasis (bilirubin greater than 10 mg/dl) the distribution of serum gangliosides was altered in different lipoprotein classes including lipoprotein X (LP(x)). The results indicate that the liver produces serum gangliosides. The diseased liver is supposed to affect the total concentration, pattern and distribution of serum gangliosides in different lipoprotein classes as a result of at least two different pathogenetic events: the qualitative and quantitative alterations of their biosynthesis and secretion into the circulation (cirrhosis); and the alteration of lipoprotein metabolism following cholestasis.

Acute Disease↗