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Biomedical subjects

A Römer

Publications and source records attributed to A Römer.

At least 19 recordsLinked to original sources
PubMed2005

[Percutaneous endovascular aneurysm repair without arteriotomy (Perclose system)].

BACKGROUND AND OBJECTIVE: It is common clinical practice to perform an arteriotomy for the endovascular treatment of infrarenal and thoracic aortic aneurysms. Instead we used the percutaneous endovascular Perclose device to perform the aneurysm repair without arterial cut-down. PATIENTS AND METHODS: The Perclose device contains four needles with two suture loops for closing the femoral artery access site. The sutures were deployed after the arterial puncture, before introduction of sheaths (diameter 12 - 27 F = 4 - 9 mm). After the procedure the sutures were used to close the puncture site. We attempted to achieve hemostasis with the Perclose system in 104 femoral arteries in 60 patients (7 females, mean age 69 +/- 12 years). The mean vessel diameter was 10 +/- 2 mm. RESULTS: The percutaneous graft implantation was successfully achieved in 58 of 60 patients. The graft could not be forwarded into the aorta in two cases because of calcified iliac arteries. The Perclose suture technique was successfully used in 97 femoral arteries. In one case a false aneurysm developed and in another case a secondary hemorrhage occurred. Seven patients needed additional manual compression to achieve complete hemostasis. A surgical repair was not necessary. The time to hospital discharge ranged from 4.5 hours to 32 days (median: 18 hours). 20 patients stayed longer than 24 h in the hospital, only 2 of them for reasons related to the puncture site. CONCLUSION: Closing the access site with the Perclose system is technically feasible and effective, even with large sheaths up to 27 F = 9 mm. This technique reduces the invasiveness of the endovascular repair of aortic aneurysms and decreases the length of hospital stay, i. e. it allows treatment in outpatients.

Adult↗
PubMed2002

Mutant prion protein acquires resistance to protease in mouse neuroblastoma cells.

Conversion of the cellular isoform of the prion protein (PrP(C)) into the pathogenic isoform (PrP(Sc)) is thought to be the causative event in prion diseases. Biochemically, PrP(Sc) differs from PrP(C) in its partial resistance to proteinase K (PK). The amino acid sequence AGAAAAGA, comprising residues 112-119 of the murine PrP(C), has been shown to be amyloidogenic and evolutionarily conserved. To assess the effect of mutations at and around this hydrophobic sequence on protease resistance, the sequence was replaced either by alanines or by glycines and, in a third mutant, a large part surrounding this region was removed. The PrP mutant carrying substitutions of glycines for alanines showed PK resistance and aberrant proteolytic processing. Tetracycline-induced expression of this mutant indicated that resistance to protease is acquired concurrent with the synthesis of the protein. These findings indicate that mutations in the central hydrophobic region lead to immediate alterations in PrP structure and processing.

Animals↗
PubMed2001

Mass spectrometric analysis reveals a cysteine bridge between residues 2 and 61 of the auxin-binding protein 1 from Zea mays L.

The major auxin-binding protein (ZmERabp1) from maize (Zea mays L.) has been structurally characterized. We determined the position of a disulfide bridge in ZmERabp1 by mass-spectrometric analysis. We show that Cys2 and Cys61 are covalently linked and that residue Cys155 bears the free sulfhydryl group. By making use of electrospray mass spectrometry, the molecular mass of ZmERabp1 was determined to be 20,243 Da comprising a sugar moiety of 1865 Da, corresponding to a high mannose-type glycan structure. Due to the high homology among all characterized ABPs, the information on the disulfide bonds will be important for functional analysis of recombinantly expressed ABP1.

Amino Acid Sequence↗
PubMed2001

Prion protein binds copper within the physiological concentration range.

The prion protein is known to be a copper-binding protein, but affinity and stoichiometry data for the full-length protein at a physiological pH of 7 were lacking. Furthermore, it was unknown whether only the highly flexible N-terminal segment with its octarepeat region is involved in copper binding or whether the structured C-terminal domain is also involved. Therefore we systematically investigated the stoichiometry and affinity of copper binding to full-length prion protein PrP(23-231) and to different N- and C-terminal fragments using electrospray ionization mass spectrometry and fluorescence spectroscopy. Our data indicate that the unstructured N-terminal segment is the cooperative copper-binding domain of the prion protein. The prion protein binds up to five copper(II) ions with half-maximal binding at approximately 2 microm. This argues strongly for a direct role of the prion protein in copper metabolism, since it is almost saturated at about 5 microm, and the exchangeable copper pool concentration in blood is about 8 microm.

Animals↗
PubMed1999

Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by a systematic approach.

In a systematic approach to the study of Saccharomyces cerevisiae genes of unknown function, 150 deletion mutants were constructed (1 double, 149 single mutants) and phenotypically analysed. Twenty percent of all genes examined were essential. The viable deletion mutants were subjected to 20 different test systems, ranging from high throughput to highly specific test systems. Phenotypes were obtained for two-thirds of the mutants tested. During the course of this investigation, mutants for 26 of the genes were described by others. For 18 of these the reported data were in accordance with our results. Surprisingly, for seven genes, additional, unexpected phenotypes were found in our tests. This suggests that the type of analysis presented here provides a more complete description of gene function.

Cell Differentiation↗
PubMed1998

Oral bioavailability of hyperforin from hypericum extracts in rats and human volunteers.

Validated analytical methods suitable for determining hyperforin in plasma after administration of alcoholic Hypericum perforatum extracts containing hyperforin are described. After oral administration of 300 mg/kg Hypericum extract (WS 5572, containing 5% hyperforin) to rats maximum plasma levels of approximately 370 ng/ml (approx. 690 nM) were reached after 3 h, as quantified by a HPLC and UV detection method. Estimated half-life and clearance values were 6 h and 70 ml/min/kg respectively. Since therapeutic doses of Hypericum extracts are much lower than that used in rats, a more sensitive LC/MS/MS method was developed. The lower limit of quantification of this method was 1 ng/ml. Using this method, plasma levels of hyperforin could be followed for up to 24 h in healthy volunteers after administration of film coated tablets containing 300 mg hypericum extracts representing 14.8 mg hyperforin. The maximum plasma levels of approximately 150 ng/ml (approx. 280 nM) were reached 3.5 h after administration. Half-life and mean residence time were 9 and 12 h respectively. Hyperforin pharmacokinetics were linear up to 600 mg of the extract. Increasing the doses to 900 or 1200 mg of extract resulted in lower Cmax and AUC values than those expected from linear extrapolation of data from lower doses. Plasma concentration curves in volunteers fitted well in an open two-compartment model. In a repeated dose study, no accumulation of hyperforin in plasma was observed. Using the observed AUC values from the repeated dose study, the estimated steady state plasma concentrations of hyperforin after 3 x 300 mg/day of the extract, i.e., after normal therapeutic dose regimen, was approximately 100 ng/ml (approx. 180 nM).

Administration, Oral↗
PubMed1998

Quality circles in ambulatory care: state of development and future perspective in Germany.

OBJECTIVE: To survey the quantitative development of quality circles (peer review groups; QC) and their moderators in ambulatory care in Germany, to describe approaches to documentation and evaluation, to establish what types of facilities and support is available and to assess opinions on the future importance of QC. DESIGN: Cross-sectional survey using a standardized questionnaire and supplementary telephone interviews. SETTING: All 23 German regional Associations of Statutory Health Insurance Physicians (ASHIP) were surveyed. RESULTS: The total number of QC in ambulatory care in Germany increased rapidly from 16 in 1993 to 1633 in June 1996, with about 17% (range 1.0-52.1%) of all practicing physicians (112 158) currently involved. Throughout Germany, 2403 moderators were trained in 168 training courses by the qualifying date. Follow-up meetings were held or being planned in 20 ASHIP, with approximately 39% (23-95%) of the moderators participating. Systematic documentation of QC work was undertaken or planned in all 23 ASHIIP, and 10 ASHIP carried out comparative evaluation, with at least five others planning to start it. The ASHIP promoted the work of QC by providing organizational (22) or financial (20) support, materials (20) or mediation of resource persons (16). Eleven ASHIP received grants from drug companies. ASHIP rated the future importance of QC as increasing (18) or stable (four), but in no case as decreasing. CONCLUSIONS AND RECOMMENDATIONS: The quantitative growth of QC in Germany is encouraging, but the extent of support and evaluation appears insufficient. Increased methodological support and facilitation, follow-up meetings on a more regular basis, improved documentation and evaluation of individual QC, and problem oriented evaluation of their impact on health care are essential for further successful development. Principles, problems and solutions discussed may be relevant for similar QI activities in other countries.

Ambulatory Care↗
PubMed1995

[Absorption of di-linoleoylphosphatidylcholine after oral administration].

Essentiale and Lipostabil contain "essential" phospholipids from the soybean, mainly 1,2-dilinoleoyl-phosphatidylcholine (CAS 998-06-1, DLPC) which is considered as the main active ingredient. A single oral dose of d15-DLPC loaded with deuterium 9 times in the choline and 6 times in the linoleic acid of the 1-position was given to volunteers. Sera from 11 blood samples taken within 48 h after application were examined by means of mass spectrometry with regard to d9-choline and d6-linoleic acid in the 1- and 2-position of serum phosphatidylcholines (PC) as well as in the serum triglycerides. d9-choline, i.e. the total of d15-PC and d9-PC, showed maximum values of 5.6% of the total serum PC concentration. Normally, about 1.3% of PC in the human serum is DLPC. Serum 1-linoleoyl-PC was increased by 32-40% after oral application of d15-DLPC. A minor uptake of d6-linoleic acid into the 2-position of serum PC, which is rich in linoleic acid, and into the serum triglycerides was observed with peak values of 2.3% and 6.1%, resp. The uptake of polyunsaturated PC species like DLPC and 1-linoleoyl-PC into the liver after oral application of drugs containing such species in high amounts like "essential" phospholipids with about 50% of DLPC let expect therapeutic effects on membranes into which this special species is incorporated.

Acylation↗
PubMed1990

[Pharmacokinetics and toxicokinetics of pentamidine in the rat following intravenous and aerosol administration].

Within the framework of toxicity studies with pentamidine aerosol the pharmacokinetics and toxicokinetics of the active substance was investigated. The plasma kinetics after intravenous administration show a strong distribution into tissues. The validity of toxicity studies was demonstrated by quantitative tissue analysis. The highest pentamidine concentrations were found in the target organ lung with a long elimination half life. The benefit of lower systemic side effects of the aerosol compared to the intravenous administration could be shown by comparative investigations. These studies were also used for doses calculations after aerosol administration.

Administration, Oral↗
PubMed1989

Chronic therapy of severe heart failure with enoximone.

Clinical trials in patients with congestive heart failure have shown a wide disparity in the hemodynamic responses to chronic therapy with newer positive inotropic drugs. Therefore, the long-term efficacy of enoximone was studied in 10 patients with severe congestive heart failure. Patients were evaluated clinically, left ventricular dimensions and contractile state were assessed by echocardiography, and exercise testing was performed at basic conditions and after 1 and 8 weeks of enoximone treatment with a daily dose between 150-300 mg. Previous therapy of heart failure was continued during the study period. Clinical symptoms of eight patients were improved after 1 week and six patients showed sustained improvement after 8 weeks of enoximone treatment. The administration of enoximone increased ejection fraction by about 25% after 1 week with a similar response after 8 weeks. Five of six patients who were able to perform exercise testing initially experienced an increased exercise capacity over the study period. The enoximone regimen was continued in the responders; after 1 year, data on three patients are available and show sustained efficacy of enoximone treatment in two patients. The administration of the drug was well tolerated without any deterioration of arrhythmias. There is evidence that oral enoximone treatment may be useful as additional therapy in patients with severe heart failure.

Aged↗
PubMed1988

A novel biologically active selenooorganic compound--VII. Biotransformation of ebselen in perfused rat liver.

Ebselen (PZ 51) is a selenoorganic compound with antioxidant and antiinflammatory properties, and its metabolism was studied in isolated perfused rat liver (hemoglobin-free, open system). 75Se-labelled ebselen was taken up into liver cells and radioactivity was excreted into bile. Biliary excretion of 75Se-compounds reached maximal values of 4 nmol/min per g wet wt. HPLC analysis of bile and effluent perfusate as well as identification of separated metabolites by mass spectrometry were carried out. The biliary metabolites were (a) an interesting novel Se-glucuronide, 2-glucuronylselenobenzanilide, (metabolite IV), as the major metabolite, and (b) an O-glucuronide, N-(4'-glucuronyloxyphenyl)-2-methylselenobenzanilide (metabolite III). The major effluent perfusate metabolites were Se-methylated derivatives (metabolites I and II). There was no evidence for sulfated metabolites. The selenodisulfide with glutathione, S-(2-phenyl-carbamoyl-phenylselenyl)-glutathione, was not detected, probably because of low steady-state concentrations and/or its biochemical lability. The selenium in ebselen is not bioavailable (e.g. for the synthesis of glutathione peroxidase), in contrast to selenite, for example, thus explaining the very low ebselen toxicity. However, the enzymatic steps in Se-methylation could be similar to those in the metabolism of selenite which include hydrogen selenide methylation. Se-glucuronides constitute a novel category of compounds in addition to the O-, N-, C- and S-glucuronide classes known in biology.

Animals↗
PubMed1988

A novel biologically active selenoorganic compound. VIII. Biotransformation of ebselen.

1. The metabolism of ebselen, a Se-containing heterocyclic compound, in rats, pigs and human volunteers has been investigated. 2. Unchanged ebselen is not present in urine, plasma or bile. All metabolites of ebselen have in common that the isoselenazolone ring is opened. 3. Both in pigs and human, the dominant metabolite in plasma and urine is a Se-glucuronide. This is the major metabolite in rats as well but, additionally, some selenomethyl-derivatives of ebselen can be detected.

Animals↗
PubMed1986

Ebselen reduces the formation of LTB4 in human and porcine leukocytes by isomerisation to its 5S, 12R-6-trans-isomer.

Ebselen, a new organoselenium compound with pronounced anti-inflammatory properties, selectively inhibits the formation of leukotriene B4 in human and porcine leukocytes with half-maximal inhibition at 4.0 and 2.7 mumol/1, respectively. The underlying mechanism was found to be a cis-trans-isomerisation of leukotriene B4 to the 5S, 12R-6-trans-isomer. 5-Hydroxy-eicosatetraenoic acid was also isomerised to the 8-trans-isomer. At higher concentrations, ebselen induces a dose-dependent decrease in the sum of total 5-lipoxygenase products with half-maximal inhibition at 30 mumol/1. Additionally, the effects of ebselen on human platelet 12-lipoxygenase and cyclooxygenase were investigated. Human platelet 12-lipoxygenase and cyclooxygenase were inhibited in a dose dependent manner with half-maximal inhibition at 20 mumol/1 and 5 mumol/1, respectively. We suggest that suppression of leukotriene B4-formation by isomerisation to a biologically inactive compound represents a promising approach to the therapy of inflammation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗