Search PubMed⌕ Search

Biomedical subjects

E Weber

Publications and source records attributed to E Weber.

At least 271 records · Page 15Linked to original sources
PubMed1989

[The relative bioavailability of paracetamol following administration of solid and liquid oral preparations and rectal dosage forms].

Determination of the Relative Bioavailability of Paracetamol Following Administration of Solid and Liquid Oral Preparations and Rectal Dosage Forms. The relative bioavailability of paracetamol from two solid and two liquid oral preparations and two rectal dosage forms, each containing 500 mg of the active ingredient, was investigated in 12 healthy male individuals. The plasma concentration-time curves of paracetamol following administration of the oral formulations were very similar; consequently there were only minor differences of the AUC0-12h (21.4, 21.9; 23.0, 22.8 micrograms.h/ml), cmax (8.8, 9.1; 10.0, 10.7 micrograms/ml), tmax (35, 25; 20, 19 min), and the terminal plasma elimination half-life t1/2 beta (2.95, 2.85; 2.86, 2.99 h) for the solid and the liquid test and reference preparations, respectively. The suppositories (test and reference formulation) differed from the oral dosage forms, but were comparable to each other with respect to AUC0-12h (18.2, 18.8 micrograms.h/ml), cmax (3.3, 3.5 micrograms/ml), tmax (1.6, 2.45 h), and t1/2 beta (3.55, 3.54 h). In all test preparations the 95% confidence limits for AUC0-12h completely were enclosed in the range of 80-120% relative bioavailability (independently of whether parametric or non-parametric statistical methods were applied); the limits for the oral formulations were quite narrow, thus indicating a highly consistent release of the active compound from the tablets as well as from the liquid dosage form. A comparison of the mean values of cmax by analysis of variance at the 80% probability level did not reveal any significant differences between the test and the corresponding reference formulations; based on non-parametric statistical methods, the 95% confidence limits for cmax were enclosed in the range of 70-130%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1989

[Isolated rupture of an iliacus aneurysm].

A retrospective analysis of 23 patients with isolated iliac aneurysms is presented. The age of the 23 men ranged from 49 to 89 years (mean +/- SE: 72.2 +/- 8.4 y). All patients had pain, nineteen (83%) were in shock, in only 11 (48%) an abdominal mass was palpable. Fifteen (65%) of the aneurysms were located in the common iliac artery, 5 (22%) in the internal and 3 (13%) in the external iliac artery. Their diameter ranged from 3 to 12 cm (mean +/- SE: 7.8 +/- 2.6 cm). Resection with an unilateral graft interposition was done in 12 (52%), a Y-graft implanted in 8 (35%) and an endoaneurysmorrhaphy of the internal aneurysm performed in 2 patients. Early mortality was 22% and was not statistically different from the 28.6% mortality in ruptured abdominal aneurysm resections performed in the same time. Because of the substantial risk of rupture with high mortality elective operative intervention should be considered for isolated iliac aneurysms with a diameter more than 3 cm.

Aged↗
PubMed1988

Difference between endothelium-dependent relaxation in arterial and in venous coronary bypass grafts.

Both the internal mammary artery and the saphenous vein are used to construct coronary-artery bypass grafts. We hypothesized that the release or production of endothelium-derived relaxing factor, which regulates blood flow and inhibits platelet function, may differ in venous and arterial grafts. We therefore studied endothelium-dependent relaxation in internal mammary arteries, internal mammary veins, and saphenous veins obtained from 58 patients undergoing coronary bypass surgery. Vascular rings with and without endothelium were suspended in organ chambers, and isometric tension was recorded. Acetylcholine (10(-8) to 10(-4) M), thrombin (1 U per milliliter), and adenosine diphosphate (10(-7) to 10(-4) M) evoked potent endothelium-dependent relaxation in the mammary artery but weak response in the saphenous vein (P less than 0.005; n = 6 to 27). In the mammary artery, relaxation was greatest in response to acetylcholine (86 +/- 4 percent reduction in norepinephrine-induced tension), followed by thrombin (44 +/- 7 percent) and adenosine diphosphate (39 +/- 8 percent). In the saphenous and mammary veins, relaxation was less than 25 percent. Relaxation was unaffected by indomethacin but was inhibited by methylene blue and hemoglobin (P less than 0.005 and 0.01, respectively), which suggests that endothelium-derived relaxing factor was the mediator. Endothelium-independent relaxation in response to sodium nitroprusside was similar in arteries and veins. We conclude that endothelium-dependent relaxation is greater in the mammary artery than in the saphenous vein. The possibility that this contributes to the higher patency rate among arterial grafts than among venous grafts will require further study.

Acetylcholine↗
PubMed1988

Characterization of metorphamide-like immunoreactivity in the zona incerta and lateral hypothalamus: co-localization with alpha-melanocyte-stimulating hormone-like immunoreactivity.

Double-staining in either vibratome or paraffin sections using contrasting chromogens revealed an alpha-melanocyte-stimulating hormone (alpha-MSH)-containing cell group in the arcuate nucleus, a metorphamide-containing cell group in the paraventricular hypothalamus, and an extensive group of magnocellular perikarya in the zona incerta (ZI) and the lateral hypothalamus (LH) that appeared to contain both antigens. Staining of adjacent paraffin sections also suggested that most (and perhaps all) of the magnocellular perikarya in the ZI and LH that contained metorphamide-like immunoreactivity also contained alpha-MSH-like immunoreactivity. Metorphamide-like immunoreactivity in the ZI and the LH was abolished by absorption of the antiserum with metorphamide but was unaffected by absorption with alpha-MSH. alpha-MSH-like immunoreactivity in the ZI and LH was abolished by absorption of the antiserum with alpha-MSH but was unaffected by absorption with metorphamide. Antisera directed against [Met5]-enkephalin (Met-ENK), [Met5]-enkephalin-Arg6,Gly7,Leu8 (ENK-8), [Met5]-enkephalin-Arg6,Phe7 (ENK-7), neuropeptide Y, and FMRF-amide did not stain magnocellular perikarya in the ZI and LH. Pretreatment of paraffin sections with trypsin resulted in the appearance of [Met5]-enkephalin-Arg6-like immunoreactivity in the ZI and LH. Pretreatment of paraffin sections with trypsin did not reveal any occult Met-ENK-, ENK-7- or ENK-8-like immunoreactivity in either the ZI or the LH. These observations indicate that magnocellular neurons in the ZI and LH contain both a metorphamide-like and an alpha-MSH-like peptide but do not express either the preproenkephalin or the prepro-opiomelanocortin48 gene.

Animals↗
PubMed1988

Five-year follow-up study of independent clinical and flow cytometric prognostic factors for the survival of patients with non-small cell lung carcinoma.

Fresh surgical specimens of tumors of 187 patients with previously untreated non-small cell lung carcinomas were investigated by means of flow cytometry. The aim of the study was to look for cellular prognostic indicators for survival times of these patients in addition to the well-known clinical prognostic factors. All patients had a minimum of 5 years follow-up. Patients with aneuploid tumors had significantly shorter survival times than did those with diploid tumors (P less than or equal to 0.001). Identical results are obtained when the analysis is restricted to just those patients with T3 tumors or to patients with metastatic tumors at time of surgery or who were classified as Stage III (P less than or equal to 0.01). These data indicate that DNA ploidy is a strong and independent prognostic factor in patients with non-small cell lung carcinoma. Patients having tumors with a high proliferative activity died significantly (P less than 0.05) earlier than patients having tumors with lower proliferative activity. As with tumor ploidy, survival time in patients with high or low proliferative tumor activities was independent of whether the patients had T3-tumors, metastases, or were in Stage III. Univariate and multivariate analyses of the data in this study demonstrate two groups of independent prognostic factors for the survival of patients with non-small cell lung carcinoma: a group of clinical factors and a group of flow cytometric factors.

Adult↗
PubMed1988

Human pharmacological studies of a defined low molecular weight heparin fraction (Fragmin) evidence for a simultaneous inhibition of factor Xa and IIa (thrombin).

The effect of a low molecular weight heparin (Fragmin) (20-80 U/kg) was studied in 10 healthy male volunteers after intravenous administration. Clotting abnormalities are extensive shortly after injection, lasting for 1-2 hours depending on heparin dosage. Dilute thrombin time, showing a close correlation to anti-F-Xa activity, is as sensitive as anti-F-Xa. The parallel time course of dilute thrombin time and anti-F-Xa activity clearly demonstrates that LMWH has an effect on F-IIa lasting as long as that of F-Xa. After subcutaneous administration clotting abnormalities are only slight with 40-60 U/kg, in contrast to the intravenous study. The platelet system remains unchanged.

Adult↗
PubMed1988

Benzbromarone disposition and uricosuric action; evidence for hydroxilation instead of debromination to benzarone.

Benzbromarone is one of the main uricosuric drugs currently used. We determined plasma concentrations of benzbromarone, bromobenzarone, and benzarone and 24 hour uric acid excretion in ten healthy individuals following fasting application of two different non-micronised benzbromarone brands. In addition we explored the influence of adjusting urinary pH to near neutral values and of concomitant food intake. Benzbromarone was more rapidly absorbed from the test preparation than from the reference preparation; the extent of systemic availability did not differ significantly. Urinary pH adjustment had no clearcut effect, whereas food intake retarded drug absorption (even though not significant because of the variability of the data). Binding of benzbromarone to plasma proteins exceeded 99%. Bromobenzarone and benzarone were not detectable and are unlikely to be major metabolites of benzbromarone. Instead we found two other compounds suggestive of metabolites, one of them being monohydroxilated benzbromarone. The plasma concentrations of the parent compound in one subject exceeded those of the rest of the group, possibly indicating genetic differences in drug metabolism. The uricosuric effect was not related to benzbromarone plasma concentrations.

Adult↗
PubMed1988

Primary structure of the uracil transport protein of Saccharomyces cerevisiae.

We present in this paper the nucleotidic sequence of the FUR4 gene encoding the uracil permease in the yeast Saccharomyces cerevisiae. The deduced amino acid sequence of the permease has 633 residues; it consists of many hydrophobic stretches, only the N-terminal and C-terminal ends of the protein (about 100 and 50 amino acids respectively) being mostly hydrophilic. No N-terminal hydrophobic signal peptide is present, although it is shown in this work that the biosynthesis of the uracil permease goes through the secretion/glycosylation pathway. Using the results of three different methods, allowing the prediction of transmembrane alpha helices in proteic sequences, we drew a model of folding of the permease in the membrane.

Amino Acid Sequence↗
PubMed1988

[Treatment and follow-up care after heart transplantation].

Today survival rates after heart transplantation of around 80% at 1 year and around 65% at 5 years are realistic. Most patients attain NYHA functional class I. Due to progress in donor and recipient selection, in immunotherapy, and in a systematic follow-up program post transplant, heart transplantation today has become an accepted treatment in special forms of terminal heart disease. Between September 23, 1985, and May 15, 1987, 19 patients were transplanted in Zurich. After an average of 7 months (1-20), 18 patients are alive with NYHA functional class I. The follow-up program checks systematically for the three main problems post transplant (rejection, infection, and drug-induced side-effects). Regular endomyocardial biopsy is the gold standard for diagnosis of rejection. Non-invasive methods, such as cyto-immunological monitoring, neopterin, or beta 2-microglobulin, are not a substitute but valuable adjunctive diagnostic methods.

Adult↗
PubMed1988

DNA and S-phase distribution and incidence of metastasis in human primary lung carcinoma.

The aim of the study was to investigate the relationship between DNA and S-phase distribution in primary non-small-cell lung carcinomas with the incidence of metastasis. Patients with non-small-cell lung carcinomas were divided into two groups depending on whether at time of surgery there were metastases or not, and these groups were correlated with the data obtained by flow cytometry or autoradiography. As expected from other studies, survival time was significantly longer for those patients without metastases at time of surgery (P = .0002) and the incidence of metastasis was significantly higher when the primary tumor was greater than or equal to 70 cm3 (P = .026). In this study, a total of 185 fresh specimens of lung carcinomas were investigated by flow cytometry. Patients with aneuploid tumors had a higher tendency to have metastases (P = .016). Patients with tumors with a higher proportion of S-phase cells measured by either flow cytometry or autoradiography demonstrated significant increase in the formation of metastases (P = .02 and P = .05). We feel that these results warrant further investigation with other primary tumors. A comparison of primary tumors that are known to rapidly metastasize vs. those that either slowly or rarely metastasize may prove to yield valuable insight into the important factors associated with metastatic potential.

Carcinoma, Non-Small-Cell Lung↗
PubMed1988

Modification of tumor cells by a low dose of Newcastle disease virus. Augmentation of the tumor-specific T cell response in the absence of an anti-viral response.

The present study elucidates the mechanism whereby viral xenogenization of highly metastatic ESb lymphoid tumor cells increases tumor immunogenicity and syngeneic tumor-specific T cell responses in comparison to nonmodified tumor cells. It was found that the frequency of cytotoxic T lymphocytes specific for the Esb tumor-associated transplantation antigen (TATA) and the cytotoxic anti-tumor activity in bulk cultures of immune spleen cells were significantly increased (by factor 3 and 25, respectively) when using virus-modified tumor cells. An amplified response was observed both in vivo and in vitro which might explain the demonstrated effectiveness of this approach for postoperative immunotherapy of ESb metastases. For the stimulation of tumor-specific cytolytic T lymphocytes (CTL) the ESb tumor cells which are highly metastatic were infected with an avirulent strain of the paramyxovirus Newcastle Disease Virus (NDV). Infection of ESb cells with low amounts of NDV was sufficient to lead to an increase in cytolytic activity of tumor-specific CTL after sensitization in vivo and restimulation in vitro. In a sensitive limiting dilution mixed leukocyte-tumor cell microculture system the direct effect of viral modification on the frequency and specificity of CTL was investigated. The number of ESb-specific CTL per spleen could be raised from about 3300 (without modification) to 9100 by both in vivo and in vitro application of ESb-NDV. One application of ESb-NDV (in vivo or in vitro) increased the number of CTL to 4900 and 4600, respectively. In split-type experiments it could be shown at the clonal level that viral modification did not alter the specificity of ESb-specific CTL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Biliary excretion of phenprocoumon and metabolites.

To evaluate phenprocoumon elimination its possible biliary excretion was evaluated in addition to the known pathway of renal elimination. Bile samples were obtained during diagnostic endoscopy in patients receiving chronic phenprocoumon therapy and were analyzed for phenprocoumon and its metabolites by HPLC and GC-MS. The following substances were detected, mainly in conjugated form: unchanged phenprocoumon and the metabolites 7-hydroxy-, 4'-hydroxy-, and 6-hydroxy-phenprocoumon. The data provide direct evidence of the biliary elimination of unchanged phenprocoumon and its metabolites in humans.

4-Hydroxycoumarins↗
PubMed1988

Evolutionary relationship and secondary structure predictions in four transport proteins of Saccharomyces cerevisiae.

The comparison of the amino acid sequences of four yeast transport proteins indicates that there is a questionable relatedness between the uracil permease (FUR4) and the purine-cytosine permease (FCY2), whereas the arginine permease (CAN1) and the histidine permease (HIP1) clearly originated from a common molecular ancestor. The analysis of the primary structure of these transport proteins by two methods of secondary structure predictions suggests the presence of 9-12 membrane-spanning alpha-helices in each polypeptide chain. These results are concordant in that 90% of the alpha-helices were determined by both methods to be at the same positions. In the aligned sequences HIP1 and CAN1, the postulated membrane-spanning alpha-helices often start at corresponding sites, even though the overall sequence similarity of the two proteins is only 30%. In the aligned DNA coding sequences of CAN1 and HIP1, synonymous nucleotide substitutions occur with very similar frequencies in regions where the replacement substitution (changing the amino acids) frequencies are widely different. Moreover, our data suggest that the replacement substitutions can be considered as neutral in the N-terminal segment, whereas the other regions are subject to a conservative selective pressure because, if compared to a random drift, the replacement substitutions are underrepresented.

Amino Acid Sequence↗
PubMed1988

Modulating influence of dehydroepiandrosterone administration on the morphology and enzyme phenotype of dimethylaminoazobenzene-induced hepatocellular foci and nodules.

The effect o 4 weeks dietary administration of the hormone dehydroepiandrosterone (DHEA) on enzyme and morphological phenotype of focal lesions previously induced by dimethylaminoazobenzene (DAB) treatment was investigated in Sprague-Dawley rats. In contrast to the DAB-alone livers where large numbers of glycogen-storing, mixed cell nodules homogeneously positive for glutathione S-transferase P form (GST-P) were apparent, DHEA treated animals were characterized by significantly fewer, more heterogeneous lesions, in some cases demonstrating increased amphophilia and structured basophilia. The enhanced heterogeneity, in some ways reminiscent of that reported earlier for 'reversibility' or 'remodelling' of rapidly induced nodular lesions, was associated with increased catalase (CAT), acid phosphatase (AP) and glucose-6- phosphatase (G6Pase) and decreased glycogen contents and phosphorylase (PHO) activity in both nodules and background parenchyma. Glucose-6-phosphatase (G6PD) activity was elevated irregularly focal lesions also demonstrating a heterogeneous reaction. The experimental data suggest two separate effects of the hormone treatment the first involving modulation of the usual altered phenotype of preneoplastic lesions with a shift towards 'tigroid' cell character and the second, similar to that reported earlier for rapidly induced nodules, involving enhanced phenotypic instability and leading to reduction in numbers.

Animals↗
PubMed1988

Synthesis and characterization of a radiolabelled derivative of the phencyclidine/N-methyl-D-aspartate receptor ligand (+) MK-801 with high specific radioactivity.

A [3H]-labelled derivative of the drug (+)MK-801 with a high specific radioactivity was synthesized by first preparing a tribromo derivative of (+)MK-801 followed by catalytic reduction in the presence of [3H]-gas and subsequent purification of the radioactive product by reversed-phase high performance liquid chromatography (RP-HPLC). This resulted in pure (+) [3H]MK-801 with a specific radioactivity of 97 Ci/mmol. The (+) [3H]MK-801 was shown to interact with high affinity and selectivity with the phencyclidine (PCP) receptor in guinea pig brain membrane suspensions. The PCP receptor is associated with a cation channel that is chemically gated by glutamate and N-methyl-D-aspartate (NMDA). Drugs that interact with the PCP receptor block this channel. The (+) [3H]MK-801 described here will be useful to investigate the biochemistry of PCP/NMDA receptors in experiments where a high specific radioactivity is essential.

Animals↗
PubMed1988

Distribution of O6-ethylguanine in DNA exposed to ethylnitrosourea in vitro as visualized by electron microscopy using a monoclonal antibody.

Application of a monoclonal antibody (Mab ER-6; Rajewsky et al., 1980) specific for O6-ethyl-2'-deoxyguanosine (O6-EtdGuo), in conjunction with a protein-free spreading procedure for double-stranded DNA molecules and transmission electron microscopy, permits the visualization of antibody molecules complexed to O6-EtdGuo residues formed in DNA upon reaction with the carcinogen N-ethyl-N-nitrosourea (EtNU) (Nehls et al., 1984). To obtain information on the distribution of O6-EtdGuo in native DNA exposed to EtNU in vitro, samples of purified rat brain DNA were briefly incubated with EtNU at concentrations differing by a factor of 8 (0.5 and 4 mg of EtNU/ml, respectively). As determined in DNA hydrolysates by competitive radioimmunoassay, the resulting DNA preparations contained O6-EtdGuo at O6-EtdGuo/2'-deoxyguanosine molar ratios of 15.1 X 10(-5) and 116 X 10(-5), respectively. Interspace distances between Mab-binding sites in both sets of ethylated DNA were determined by electron microscopy both in individual DNA fragments of different size, and in computer-generated, long-thread DNA constructs. Comparative statistical analyses by a newly developed MOLRANDO computer program show a non-random distribution pattern of Mab-binding O6-EtdGuo residues.

Animals↗