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Biomedical subjects

H Wieland

Publications and source records attributed to H Wieland.

At least 19 recordsLinked to original sources
PubMed1992

Heterozygosity for the IVS-I-5 (G-->C) mutation with a G-->A change at codon 18 (Val-->Met; Hb Baden) in cis and a T-->G mutation at codon 126 (Val-->Gly; Hb Dhonburi) in trans resulting in a thalassemia intermedia.

We have analyzed the hemoglobins of a young German patient with beta-thalassemia intermedia and of his immediate family and included in these studies an evaluation of possible nucleotide changes in the beta-globin genes through sequencing of amplified DNA. One chromosome of the propositus and one of his father's carried the GTG-->GGG mutation at codon 126 leading to the synthesis of Hb Dhonburi or alpha 2 beta (2)126(H4)Val-->Gly; this variant is slightly unstable and is associated with mild thalassemic features. His second chromosome and one of his mother's had the common IVS-I-5 (G-->C) mutation that leads to a rather severe beta(+)-thalassemia and the GTG-->ATG mutation at codon 18, resulting in the replacement of a valine residue by a methionine residue. This newly discovered beta-chain variant, named Hb Baden, was present for only 2-3% in both the patient and his mother. This low amount results from a decreased splicing of RNA at the donor splice-site of the first intron that is nearly completely deactivated by the IVS-I-5 (G-->C) thalassemic mutation. The chromosome with the codon 18 (GTG-->ATG) and the IVS-I-5 (G-->C) mutations has thus far been found only in this German family; analysis of 51 chromosomes from patients with the IVS-I-5 (G-->C) mutation living in different countries failed to detect the codon 18 (GTG-->ATG) change.

Amino Acid Sequence↗
PubMed1992

[The long-term therapy of familial hypercholesterolemia with heparin-induced extracorporeal LDL precipitation].

The long-term tolerance to and effectiveness of heparin-induced extracorporeal LDL precipitation (HELP) in combination with lipid reducing drugs and diet was tested in six patient (5 males, 1 female; mean age 48 +/- 4 years). Follow-up period was over 50 months, in one patient over 24 months, while one man had a sudden cardiac death 57 weeks after starting treatment. The study was divided into three phases. In phase I (24 months) treatment consisted of HELP and conventional lipid-reducing drugs; in phase II (12 months) of lovastatin (80 mg daily) and cholestyramine (12-24 g daily); and phase III (14 months) of HELP, lovastatin and cholestyramine. In phase I it was possible to lower the pre-treatment level of LDL-cholesterol from 306 +/- 18 mg/dl to 173 +/- 13 mg/dl (43.5%). A similar effect (from 307 +/- 21 mg/dl to 155 +/- 17 mg/dl [-49.5%]) was obtained in phase II. The resumption of HELP reduced the pre-treatment LDL concentration to 136 +/- 9 mg/dl (-55.7%). The various treatment regimens were well tolerated. Biochemical data remained unchanged except for iron loss requiring substitution. Thus combined HELP, lovastatin and ion exchange offer for the first time an effective and reliable means in familial hypercholesterolaemia of clearly reducing long-term the mean LDL cholesterol level below the atherosclerosis threshold of 120 mg/dl.

Anticholesteremic Agents↗
PubMed1992

Biosynthesis and excretion of gangliosides by the isolated perfused rat liver.

De novo synthesis and excretion into perfusate and bile fluid of hepatic gangliosides were studied in isolated perfused rat livers. Addition of N-acetyl-[6-3H(n)]D-mannosamine to the perfusate resulted in radioactive synthesis of at least eight gangliosides labeled in their sialic acid residues. About 10% of total de novo synthesized gangliosides were excreted into the perfusate, less than 1% into the bile fluid. Labeled gangliosides were tentatively identified by cochromatography with known standards. All of them are known to occur in rat liver and sera. The results indicate that most, if not all, normal serum gangliosides are synthesized in the liver; excretion with bile fluid is negligible. They explain previous observations, and indicate clinical implications, which are discussed.

Animals↗
PubMed1992

Coupling of m-aminophenylboronic acid to s-triazine-activated Sephacryl: use in the affinity chromatography of glycated hemoglobins.

An improved process is described for covalent coupling of m-aminobenzeneboric acid to s-triazine-activated Sephacryl matrices. The derivatized Sephacryl gel contained up to 150-200 mumol boronate per ml. It has been applied to the separation of glycated and non-glycated hemoglobins (Hbs) present in red-cell hemolysate. The new bioaffinity support was evaluated by the analysis of 67 diabetic patients and 20 normal adults. The mean value for glycated Hb was 6.6 +/- 0.8% for non-diabetics and 11.2 +/- 2.9% for diabetics. The method effects group-specific separation between glycated and non-glycated Hbs even in presence of foetal Hb and abnormal Hb variants. There is an excellent correlation between the glycated Hb levels obtained by the new method and two established procedures, namely high-performance liquid chromatography (r = 0.933) and affinity Merckotest (r = 0.991). The inter-assay and intra-assay coefficient of variations of less than 3.0% suggest that the method is reproducible. The results indicate that the method may serve as an alternative procedure for the study of glycated proteins. The s-triazine-activated Sephacryl could also be used for immobilizing enzymes and for preparing biospecific absorbents.

Acrylic Resins↗
PubMed1992

Human serum gangliosides in hypercholesterolemia, before and after extracorporeal elimination of LDL.

Total content, pattern and transport by lipoproteins of gangliosides have been studied in the sera of 10 patients with hypercholesterolemia and manifest cardiovascular disease. Half of the patients with hypercholesterolemia and 3 healthy controls were treated with heparin-induced extracorporeal LDL precipitation (HELP). In the sera of the untreated group total gangliosides and cholesterol were elevated about 2-fold. Ratios of normal ganglioside components were not altered and abnormal ganglioside species not detected. Treatment with HELP resulted in an almost selective removal of lipid-bound sialic acid carried on LDL. The re-increase of total serum gangliosides was strictly correlated to that of LDL-cholesterol and apolipoprotein B. Total gangliosides and ratios of individual components carried on single LDL- and HDL-particles were not altered by the HELP treatment. Our results indicate that gangliosides are excreted into the serum along with nascent apolipoprotein B-containing lipoproteins, which are of hepatic origin. In hypercholesterolemia excretion of gangliosides into the circulation is elevated and surplus of circulating gangliosides is bound to increased numbers of 'atherogenic' LDL. Biosynthesis of different ganglioside components, most probably by the liver, and total amount of gangliosides bound to lipoprotein particles seem not to be altered.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

[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↗
PubMed1991

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↗