PubMed Health⌕ Search

Biomedical subjects

A Müller

Publications and source records attributed to A Müller.

At least 397 records · Page 22Linked to original sources
PubMed1993

Pharmacodynamics and pharmacokinetics of oral nitrendipine solution in hypertensive patients with advanced renal failure.

Nitrendipine solution 5 mg.ml-1 in the dose of 5 mg was given orally to 20 patients with chronic renal failure and elevated diastolic blood pressure (> or = 110 mmHg), of whom 10 were on maintenance haemodialysis (endogenous creatinine clearance < 5 ml.min-1) and 10 were at the predialysis stage (endogenous creatinine clearance 5-20 ml.min-1). The aim of the study was to investigate the influence of kidney function and/or dialysis treatment on the pharmacokinetic and pharmacodynamic profile of a solution of nitrendipine and to assess its antihypertensive efficacy. After 10 min there was a significant reduction in blood pressure from 188/113 to 173/100 (patients not dependent on dialysis) and from 197/112 to 161/94 mmHg (patients dependent on dialysis). The maximum fall in blood pressure (approximately 30%) was attained after 90 min in the dialysis patients and after 120 min in the non-dialysis group. Blood pressure increased again about 3 h after the administration of nitrendipine but it was still below baseline after 12 h. The terminal elimination half-life (4.1 h in the dialysis patients and 3.6 h in non-dialysis patients) was similar to that observed in patients with normal renal function. The pharmacokinetics of nitrendipine did not differ between the dialysis and non-dialysis groups. There was a correlation between plasma concentration and the blood pressure reduction. The maximum plasma concentration of nitrendipine was reached after 0.5 h (median) and did not differ between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Polymorphism of glutathione conjugation of methyl bromide, ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchanges (SCE) in lymphocytes.

A hitherto unknown glutathione-S-transferase in human erythrocytes displays polymorphism: three quarters of the population ("conjugators") possess, whereas one quarter ("non-conjugators") lack this specific activity. A standard method for the identification of conjugators and non-conjugators with the use of methyl bromide and gas chromatography (head space technique) is described. Three substrates of the polymorphic enzyme, methyl bromide, ethylene oxide and dichloromethane (methylene chloride), were incubated in vitro with individual whole blood samples of conjugators and non-conjugators. All three substances led to a marked increase of sister chromatid exchanges (SCE) in the lymphocytes of the non-conjugators but not in those of conjugators. A protective effect of the glutathione-S-transferase activity in human erythrocytes for the cytogenetic toxicity of these chemicals in vitro is thus confirmed. Since the enzyme activity is not found in erythrocytes of laboratory animals, species extrapolations for risk assessment of methyl bromide, ethylene oxide and dichloromethane should be reconsidered.

Erythrocytes↗
PubMed1993

Molecular cloning of an echinococcal microtrichal antigen immunoreactive in Echinococcus multilocularis disease.

A cDNA expression library of the larval stage of the cestode worm Echinococcus multilocularis has been established in the phage lambda ZAPII system. By immunoscreening with pooled sera from patients with alveolar echinococcosis an immunoreactive clone, termed pEM13, was isolated. EM13 was expressed using the expression vector pGEX-3X, resulting in the synthesis of a glutathione S-transferase fusion protein. 82% of the sera from 28 patients suffering from E. multilocularis disease had antibodies against EM13, whereas none of the 55 sera obtained from Echinococcus granulosus-infected patients and none of the 15 sera from patients with other helminthic infections reacted with recombinant EM13. By use of a polyclonal rabbit anti-EM13 hyperimmune serum native EM13 protein could be detected only in the protoscolices of E. multilocularis, but not in E. granulosus larvae or hydatid fluid. Immunoelectron microscopy suggested that EM13 is located in the microtriches on the surface of the larvae. In contrast, EM13 mRNA could be detected by Northern blot analysis in both E. multilocularis and E. granulosus larval RNA preparations. Nucleotide and amino acid sequence analysis of a cDNA clone coding for the corresponding antigen of E. granulosus larvae, termed EG13, revealed a 21-bp insertion, a 51-bp deletion and additional 22 nucleotide exchanges resulting in a 96.3% identity at the nucleotide sequence level and a 96.6% identity at the amino acid sequence level to the coding region of the cDNA pEM13. Cross-reactivity of the polyclonal anti-EM13 serum with the recombinant EG13 indicates a posttranscriptional regulation mechanism, resulting in an EG13 negative phenotype in E. granulosus.

Amino Acid Sequence↗
PubMed1993

Successful treatment of ongoing intestinal allograft rejection permits recovery of graft structure and function.

Acute rejection episodes often complicate clinical small bowel transplantation, which prompted us to investigate whether such episodes can be reversed and the intestinal graft salvaged. Inbred Lewis rats that received fully allogeneic Brown-Norway small bowel allografts were treated with cyclosporin A (10 mg/kg) for 5 days, and the drug was then discontinued. Clinical and histologic signs of acute rejection developed, and the animals were subsequently treated with FK 506 (2 mg/kg) on days 14, 16, and 18. Survival was significantly prolonged (201.7 +/- 46.8 days) when compared with animals that were not administered FK 506 (16.5 +/- 0.8 days) or allograft recipients that received no immunosuppressive therapy (10.8 +/- 0.7 days). The histologic changes and functional impairment due to rejection that were observed prior to the start of the FK 506-therapy were reversed. However, biopsy specimens of all animals exhibited features of chronic rejection. This study provides evidence that acute rejection of intestinal allografts can be successfully treated with a short course of FK 506.

Acute Disease↗
PubMed1993

Tetragalloylquinic acid, the major antiasthmatic principle of Galphimia glauca.

In the search for antiasthmatic principles in plant drugs, a bioguided fractionation of an alcoholic extract of Galphimia glauca was performed using a plethysmographic in vivo model. Tetragalloylquinic acid (G1), which was found together with other compounds (gallic acid, methyl gallate, ellagic acid, and flavonoid acylglycosides), showed the highest activity against bronchial hyperreactivity and allergic reactions. Using mass and NMR spectroscopy in combination with energy calculations, the structure G1 was elucidated as tetra-O-galloylquinic acid. Depending on the solvent used, the quinic acid skeleton can occupy a fixed conformation or several interconverting ones on the NMR time scale.

Animals↗
PubMed1993

Ventral brain stem schwannoma at the entry zone of the hypoglossal nerve.

The unusual case of a ventral brain stem schwannoma located at the entry zone of the hypoglossal nerve in a 49-year-old woman is reported. The diagnosis of a schwannoma was confirmed histologically after partial tumor resection via the dorsolateral, suboccipital, transcondylar approach. Hypotheses for the pathogenesis of intramedullary schwannomas are discussed.

Brain Stem↗
PubMed1993

Thy-1 tk transgenic mice with a conditional lymphocyte deficiency.

Thy-1 has been used as a cell surface marker for identification of mature T cells, T lymphoid precursors and the hematopoietic stem cell. The developmental program of these cells during hemato/lymphopoiesis is complex because of heterogeneity of the populations and subsequent migration. To study the differentiation of Thy-1 positive cells at precise periods of in vivo development we have used a strategy based on cell specific toxicity. In the transgenic mouse studies presented here, Thy-1 positive cells are ablated by targeting the expression of the conditional toxin Herpes simplex virus 1 thymidine kinase (tk) with Thy-1 transcriptional control elements. We demonstrate the controlled expression of HSV1 tk in Thy-1 expressing cells of adult transgenic mice and the conditional ablation of > 90% of maturing thymocytes. We describe the distinct subpopulations of cells remaining within individual ablated thymuses and show by phenotypic analyses that Thy-1 tk induced ablation enriches for CD4 low and double negative thymocytes. Furthermore, we demonstrate a differential effect of thymus directed ablation on the maturing peripheral T cell compartment at various times in mouse development. This strategy is successful for production of a conditional T lymphocyte deficiency and could be useful in the study of T lineage development and direct in vivo isolation of enriched T precursor cell populations.

Animals↗
PubMed1993

Phospholipid substitution of capsular polysaccharides and mechanisms of capsule formation in Neisseria meningitidis.

Within the capsule gene complex (cps) of Neisseria meningitidis two functional regions B and C are involved in surface translocation of the cytoplasmically synthesized capsular polysaccharide, which is a homopolymer of alpha-2,8 polyneuraminic acid. The region-C gene products share characteristics with transporter proteins of the ABC (ATP-binding cassette) superfamily of active transporters. For analysis of the role of region B in surface translocation of the capsular polysaccharide we purified the polysaccharides of region B- and region C-defective Escherichia coli clones by affinity chromatography. The molecular weights of the polysaccharides were determined by gel filtration and the polysaccharides were analysed for phospholipid substitution by polyacrylamide gel electrophoresis and immunoblotting. The results indicate that the full-size capsular polysaccharide with a phospholipid anchor is synthesized intracellularly and that lipid modification is a strong requirement for translocation of the polysaccharide to the cell surface. Proteins encoded by region B are involved in phospholipid substitution of the capsular polysaccharide. Nucleotide sequence analysis of region B revealed two open reading frames, which encode proteins with molecular masses of 45.1 and 48.7 kDa.

Amino Acid Sequence↗
PubMed1993

Coordinate increase in activity of proteinase subunits of the 1300-kDa megaproteinase of Frankia strain BR: role of carbon source depletion and extracellular metabolites.

We have recently described the presence of a high molecular mass multicatalytic proteinase complex (megaproteinase; 28 S, 1300 kDa) in Frankia strain BR. The complex dissociates into 11 low molecular mass proteinase subunits (40-19 kDa) when subjected to sodium dodecyl sulfate - gelatin - polyacrylamide gel electrophoresis. We show here that the activity of these proteinase subunits strongly increased after cessation of growth in stirred BAP-PCM mineral medium. Subsequent addition of either BAP medium components or sodium propionate alone, as carbon source, to a Frankia culture at the end of the exponential growth phase was found to prolong growth for 1 additional day, and to delay the increase in activity of the proteinase subunits for 3 days after cessation of growth. Addition of ammonium chloride alone, as nitrogen source, had no effect. On the other hand, when Frankia cells in the late exponential phase (3 days) were resuspended in a culture filtrate recovered from a 5-day-old culture and supplemented with BAP-PCM medium components, the biomass yield decreased to about 50%. Also, the activity of the proteinase subunits increased as soon as growth ceased. The ability of this culture filtrate to inhibit growth and stimulate the activity of proteinase subunits was partially lost by heating or was largely removed by DEAE-cellulose treatment. Thus, our findings indicate an extracellular control of Frankia megaproteinase activity, suggesting that carbon source depletion and probably accumulation of heat-sensitive growth-inhibiting metabolites in the medium are determining factors.

Carbon↗
PubMed1993

Comparative study on the proarrhythmic effects of some antiarrhythmic agents.

BACKGROUND: A main side effect of antiarrhythmic drug therapy is the tendency of these drugs to promote arrhythmia within the therapeutic concentration range, i.e., the proarrhythmic activity of these drugs. However, a model for in vitro assessment, quantification, and comparison of proarrhythmic drug activities was still lacking, and only sparse data were available. METHODS AND RESULTS: To analyze the arrhythmogenic risk of common antiarrhythmic drugs in a quantitative and comparative manner, isolated perfused rabbit hearts were treated with increasing concentrations of antiarrhythmic drugs corresponding to low, medium, and high therapeutic concentrations. For analysis of the epicardial activation process, an epicardial mapping (256 unipolar leads) was performed. For each electrode, the activation time was determined. From these data, the origins of epicardial activation ("breakthrough points" [BTP]) were determined. At each electrode, an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similarity of various heartbeats (under treatment) compared with control was evaluated by determination of the percentage of identical BTPs (deviation < or = 1 mm) and of similar VECs (deviation < or = 5 degrees). BTP and VEC were reduced by all antiarrhythmic agents tested (propafenone = flecainide > quinidine > ajmaline > procainamide > disopyramide > mexiletine = lidocaine > sotalol), indicating a more or less pronounced disturbance of the epicardial activation process. Treatment with propafenone, quinidine, and disopyramide and to a lesser extent sotalol prolonged the activation-recovery interval (ARI). ARI dispersion was greatly enhanced by flecainide and was reduced by sotalol. In addition, it could be shown that propranolol is able to reduce the proarrhythmic action of flecainide. This effect seemed to be due to a reduction of the flecainide-induced increase in ARI dispersion. CONCLUSIONS: From the results of our study, we propose the following rank order of the arrhythmogenic risk: flecainide > propafenone > quinidine > ajmaline > disopyramide > procainamide > mexiletine, lidocaine > sotalol. Moreover, we conclude that propranolol given additionally may be helpful in reducing the proarrhythmic risk of flecainide.

Animals↗
PubMed1993

[Isolation and characterization of hepatocytes from chronic cholestatic damage to rat livers after bile duct ligation].

The aim of these investigations was the isolation and characterisation of hepatocytes from chronic injured rat livers after bile duct ligation. In three months old female Uje:WIST rats the distal common bile duct was double ligated. 14 days after the ligation 80% of the rats survived. The content of hepatic OH-prolin was increased in relation to shamoperated control animals. The histological examination showed a marked fibrous and oedematous spreading of the portal tract as well as an extensive bile duct proliferation after 14 days. A correlation between OH-prolin content of the liver and index of fibrosis was found. 14 days after ligation the hepatocytes were isolated according to Seglen (7). The yield of hepatocytes isolated from the liver of cholestatic rats and from control animals was on average 4 x 10(8) cells with a viability of 80%. Ultrastructural the most hepatocytes showed intact organells without injury. We can conclude, that it is possible to isolate hepatocytes from chronic cholestatic rat livers with a good yield and viability as well as with an intact ultrastructure. These cells are suitable for additional metabolic investigations.

Animals↗
PubMed1993

[Recovery of psychomotor and cognitive functions following anesthesia. Propofol/alfentanil and thiopental/isoflurane/ alfentanil].

Recent changes in the medical system have resulted in a significant increase of ambulatory surgical procedures. Therefore, a safe and short postoperative recovery period and, especially, the full recovery of complex psychological function after general anaesthesia have become increasingly important. In the present study we investigated the recovery of psychomotor and cognitive function after general anaesthesia with propofol/alfentanil and thiopentone/isoflurane/alfentanil. PATIENTS AND METHODS. Institutional approval and informed consent was obtained in 40 female ASA I or II patients undergoing diagnostic laparoscopy. As oral premedication the patients received chloracepat (10-20 mg) 45 min before the start of anaesthesia. Anaesthesia was induced in group I with propofol (2.5 mg/kg) and maintained with propofol (6-12 mg/kg/h)/alfentanil (0.05 mg/kg) and 50% N2O in O2. The patients of group II received thiopentone (5 mg/kg) for induction and isoflurane (0.5-1.5 vol%)/alfentanil (0.05 mg/kg) and 50% N2O in O2 for maintenance of general anaesthesia. In particular we measured the following parameters: (1) The recovery time, defined as the interval between the termination of the anesthetic and the patient's correct recall of her birth date. (2) The choice reaction times to optical stimuli (red or green light), which was used as a parameter for attention and psychomotor function. (3) The score in the "Zahlen-Verbindungs-Test" in which the patients had to connect numbers from 1 to 90 in correct order. This is also a parameter to quantify attention and psychomotor function. (4) The digit span which is a value derived from the number of correctly reproduced digits from a list presented to the patients. It is a measure of numerical memory. (5) The Munich Verbal Learning Test, which is the German version of the California Verbal Learning Test. It represents the number of correctly reproduced words from a previously presented list and is a measure of the verbal memory. (6) The Wisconsin Card Sorting Test, which serves to test the ability to plan and act and to form terms and concepts. (7) The State-Trait Anxiety Inventory, to quantify state anxiety. (8) Pain score, using a visual analogue scale. The tests were performed at four measurement points: the day before the operation and 30, 60, and 240 min after recovery. The "Zahlen-Verbindungs-Test", the digit span and the Munich Verbal Learning Test were presented in four parallel forms to minimize learning effects. For statistical analysis of the data the Wilcoxon test was employed within groups and the Mann-Whitney test between groups. RESULTS. The groups were comparable in age, weight, height and level of education. No significant difference was found between them in operation or anaesthesia time or in the total dosage of alfentanil. Recovery time in the propofol group was, at 10 min, significantly shorter than in the isoflurane group, with 16 min. Choice reaction times were significantly increased 30 min after recovery from anaesthesia in both groups. In the propofol group they returned to normal after 60 min, whereas in the isoflurane group significant increases could be observed even 240 min after recovery from the anaesthetic. Choice reaction times were significantly longer in the isoflurane group than in the propofol group 60 min and 240 min after anaesthesia. In the "Zahlen-Verbindungs-Test" the patients showed significantly worse results 30 min and 60 min after anaesthesia. The propofol group tended to be better than the isoflurane group, but the difference did not reach statistical significance. Also in the digit span, the scores were significantly lower 30 min after recovery from the anaesthetic. Here again the propofol group tended to be a little better than the isoflurane group 30 min, 60 min and 240 min after anaesthesia. In the Munich Verbal Learning Test both groups had lower scores 30 min and 60 min, the isoflurane group also 240 min, after recovery...

Adult↗
PubMed1993

[Revoking the driver's license, assessment of driver competence, re-education and therapy in alcohol offenses: approaches to a necessary reorientation].

After representing figures and facts about drinking behaviour and drinking-driving offences of the 45 mio. drivers in Germany counter-measures for DWI-offenders are dealt with. The proceedings practised so far are critically analysed and new approaches are discussed. Primarily reviewed are special preventive measures and here particularly the selection procedure usually applied in Germany, in which on demand of the driver licensing authorities the question is to be answered by expert opinions whether there is to be reckoned with driving under the influence in die future, too. It is pointed out that the expert opinions are not valid enough for making a distinct decision in an individual case. Validity coefficients obtained in evaluation studies lie between phi = 0 and .28, raising the expectancy value of 50% resulting by chance at best only on to 65%. Moreover the psychological interview is understandably burdened with faked answers of the explored person, in several cases increased by a specific, professionally managed preparation for the testing situation. As a way out of the dilemma expert opinions prognosticating driver behaviour should be waived in favour of making diagnoses and proposals for treatment. The timing of regranting the driver license is then only determined by the revocation period pronounced by the court and by the performance of the measures recommended by the experts and demanded by the licensing authority. As a support for such a procedure a more consistent and resolute administration of the judicial revocation of driver license with longer periods for repeaters should be provided. Besides there is necessary a wider range of rehabilitation programs for drivers with alcoholic problems.

Accidents, Traffic↗
PubMed1992

[Monotherapy with the ACE-inhibitor ramipril or the calcium antagonist nitrendipine in essential hypertension].

Angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists have, by reason of their potentially favourable pharmacological profile, become increasingly established in the treatment of hypertension in recent years. In a double-blind randomized study with an initial placebo phase, carried out by practising physicians and thus aimed at the "usual" practice patients with essential hypertension, we assessed (1) the antihypertensive effect and tolerability of an ACE inhibitor (ramipril, 5 mg/d) or a calcium antagonist (nitrendipine, 20 mg/d) given in a single daily dose, and (2) a possible age-dependent blood pressure (BP) effect of these therapies. In the 4 weeks' placebo phase, the two treatment groups were comparable as regards average age (49.6 and 49.4 years), age-range (27-67 and 25-64 years) and BP. Fifty-two patients completed the following 6 weeks' phase with active drug therapy. On ramipril (n = 26), the BP measured 24-25 hours after the last drug administration was reduced in the supine position from an average of 155/102 to 142/91 mmHg (mean reduction -10.1%) and in the upright position from 156/106 to 141/96 mmHg (-9.3%). Nitrendipine (n = 26) reduced the average BP from 155/102 to 147/94 mmHg (-6.8%) and from 155/106 to 146/99 mmHg (-6.6%) respectively. BP-lowering effects of both treatments were largely independent of age. Including the patients who discontinued the study prematurely because of side effects (1 on ramipril, 4 on nitrendipine), the "intention to treat analysis" shows BP normalization rates (diastolic < or = 90 mm Hg) of 55% (ramipril) and 30% (nitrendipine) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗