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P Müller

Publications and source records attributed to P Müller.

At least 19 recordsLinked to original sources
PubMed1995

Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure.

Heart failure is commonly associated with high plasma concentrations of endothelin-1, a powerful vasoconstrictor produced by endothelium. The role of endogenously released endothelin-1 in the maintenance of vascular tone in chronic heart failure was assessed by acute administration of an endothelin receptor antagonist, bosentan. 24 patients with chronic heart failure received randomly and double blind two intravenous infusions of either placebo or bosentan (100 mg followed after 60 min by 200 mg). Systemic haemodynamics and plasma endothelin-1 and big-endothelin-1 concentrations were determined before and repeatedly during the 120 min observation period. Baseline endothelin-1 and big-endothelin-1 concentrations, which were above the normal range in all patients, correlated directly with the extent of pulmonary hypertension, with left and right heart filling pressures, and with pulmonary vascular resistance and inversely with cardiac index. Compared with placebo, bosentan reduced mean arterial pressure by 7.7% (95% CI 7.1-9.7), pulmonary artery pressure by 13.7% (10.5-16.9), right atrial pressure by 18.2% (12.0-24.4), and pulmonary artery wedged pressure by 8.6% (5.3-12.0); it increased cardiac index by 13.6% (9.1-18.2), decreased systemic vascular resistance by 16.5% (13.2-19.8), and decreased pulmonary vascular resistance by 33.2% (22.4-44.0). Heart rate did not change. Plasma endothelin-1 concentrations rose more than twofold from baseline in bosentan recipients while big-endothelin-1 concentrations were unchanged. These findings indicate that, in patients with chronic heart failure who have high circulatory endothelin-1 concentrations, this peptide contributes to maintenance of vascular tone. The acute haemodynamic effects of bosentan suggest that chronic endothelin antagonism could be beneficial in such patients.

Adult↗
PubMed1995

An improved assay for measuring the transverse redistribution of fluorescent phospholipids in plasma membranes.

The internalization of fluorescent 7-nitro-2,1,3-benzoxadiazol-4-yl (NBD)-phospholipids from the plasma membrane can be assessed by the irreversible quenching of analogues in the outer leaflet by dithionite. Here we have utilized this assay to follow the redistribution of short-chain C6-NBD-sphingomyelin and C6-NBD-phosphatidylserine from the cell membrane of human gingiva fibroblasts. The significant uptake of dithionite across the plasma membrane and the subsequent reduction of NBD-analogues exposed to the cytoplasmic lumen does not allow an accurate measurement of the amount of internalized lipid probes even at low temperature. We could show that a precise determination can be achieved by extraction of analogues remaining in the exoplasmic half by a short pretreatment with bovine serum albumin prior to addition of dithionite. The fluorescence of those analogues localized to the cytoplasmic lumen was slowly destroyed by permeating dithionite. The fluorescence of those NBD-probes which are localized in the inner layer of intracellular vesicles remained almost unaffected in the time course of the assay. Thus, this approach allows to distinguish between different routes of internalization of NBD-phospholipids from the plasma membrane.

4-Chloro-7-nitrobenzofurazan↗
PubMed1995

[Status of ranitidine in eradication of Helicobacter pylori].

Permanent removal of Helicobacter pylori leads to a dramatic drop in the recurrence rate of peptic ulcers. The NIH Consensus Conference recommends that Hp-positive patients with duodenal or gastric ulcer should undergo eradication treatment. To date, however, there is no consensus on what constitutes optimal eradication treatment. Presently available therapy may be triple (bismuth plus two antibiotics), dual (acid inhibition and one antibiotic) or modified triple therapy (acid inhibition and two antibiotics). Among numerous treatment proposals, results gained with the H2 blocker ranitidine stand out, on account of the double-blind nature of the studies and the adequate number of cases involved. With modified triple therapy (300 mg ranitidine nocte and 3 times 750 mg amoxicillin daily) eradication rates ranging from 85 to 90%, and with dual therapy (600 mg ranitidine and 2 g amoxicillin daily) 60 to 65%, are obtained.

Amoxicillin↗
PubMed1995

HPV DNA and p53 alterations in oropharyngeal carcinomas.

We have examined a series of 37 oropharyngeal squamous cell carcinomas for the presence of HPV 6/11, 16, and 18 DNA by polymerase chain reaction (PCR)/Southern blotting and for p53 alterations by immunohistochemistry and mutation screening with temperature gradient gel electrophoresis (TGGE). HPV sequences were found in a total of 26 of 37 cancers (70.3%), most frequently HPV 16 (20/37) followed by HPV 18 (11/37). Double infections with HPV 16 and 18 were present in 5 tumours. p53 accumulation was detectable immunohistochemically in 21 of 37 carcinomas (56.8%). There were remarkable differences in the distribution of immunoreactive tumour cells in relation to the tumour grade. A mutation screening for p53 by TGGE, directed to the amplified exons 5-8, revealed p53 mutations in 14 of 37 carcinomas (37.8%). Mutations in two different exons were present in 3 tumours, 11 tumours being hit once. Exon 7 was mutated in 6 carcinomas, exons 5 and 8 in 4 cases, and exon 6 in 3 cases. When grouping the tumours with p53 mutation according to their HPV state, HPV-positive cases showed slightly more mutations (11/26) than HPV-negative cases (3/11). Only 5 of 37 carcinomas (13.5%) contained neither HPV DNA nor p53 alterations. Our results indicate that high-risk HPV and p53 mutations frequently coexist in oropharyngeal carcinomas, in contrast to genital tumours, notably carcinomas of the cervix uteri. This may reflect different pathways in carcinogenesis in squamous cell epithelium from different sites.

Adult↗
PubMed1995

Combined FISH painting and harlequin staining for cell cycle-controlled chromosome analysis in human lymphocytes.

We present a simple method that allows scoring of FISH-painted chromosomes exclusively in the first division human lymphocytes. It consists of a combination of FISH with chromosome-specific libraries and a differential sister chromatid staining after BrdU treatment of lymphocyte cultures. The method allows a precise quantification of induced chromosome damage for human biodosimetry.

Cell Cycle↗
PubMed1995

Chromosome painting in highly irradiated Chernobyl victims: a follow-up study to evaluate the stability of symmetrical translocations and the influence of clonal aberrations for retrospective dose estimation.

Follow-up fluorescence in situ hybridization (FISH) measurements of symmetrical translocations were performed in peripheral blood lymphocytes from 12 highly irradiated victims of the Chernobyl nuclear power plant accident biannually, between September 1991 and July 1994, to investigate the persistence of these aberration type with time post-exposure. Translocations were determined using biotin-labelled painting DNA probes for human chromosomes 1, 4 and 12 and a digoxigenin-labelled alpha-satellite pancentromeric DNA probe. In 11 of 12 cases the translocation frequencies remained fairly constant during the observation period, which allows to generate comparable dose estimates on the various sampling times. In one case (no. 9) the existence of a cell clone containing the consistent chromosome rearrangement t(1;13) (q25;q14) was identified using FISH in rehybridized slides with a digoxigenin-labelled painting DNA probe for chromosome 13 and a separate G-banding analysis. To obtain reliable dose estimates, total translocation frequency has to be corrected for the high contribution (16.5-23.5%) of this clonal translocation.

Accidents↗
PubMed1995

Recurrent nasopharyngeal tumors: preliminary clinical results with interventional MR imaging--controlled laser-induced thermotherapy.

PURPOSE: To evaluate magnetic resonance (MR) imaging-controlled laser-induced thermotherapy (LITT) in the treatment of recurrent head and neck tumors. MATERIALS AND METHODS: Six patients with recurrent nasopharyngeal tumors (squamous cell carcinoma [n = 4], pleomorphic adenoma [n = 2]) underwent LITT with local anesthesia. A 7-F introducing sheath was inserted into the center of the tumor followed by a specially designed laser emitter. Therapy was monitored on-line with MR thermometry, and the amount of necrosis was estimated with dynamic and static contrast material-enhanced sequences. RESULTS: All procedures were well tolerated with use of local anesthesia, with no clinically relevant side effects. MR thermometry depicted up to 15-mm-diameter areas of less signal intensity near the laser tip. Coagulative necrosis was achieved in all patients (volume range, 4-28 cm3), and clinical symptoms were reduced in four. CONCLUSION: MR imaging-controlled LITT may be a safe, minimally invasive alternative in the treatment of recurrent head and neck tumors.

Adenoma, Pleomorphic↗
PubMed1995

[Protective effects of ranitidine in ibuprofen gastroduodenopathy. An endoscopic controlled double blind study].

Protective Effect of Ranitidine in Ibuprofen Gastroduodenopathy/An endoscopically controlled double-blind study in healthy volunteers. In a randomized parallel double-blind study the gastroduodenal effects of 600 mg ibuprofen racemate (CAS 15687-27-1) tid in the presence of 150 mg ranitidine (CAS 66357-35-5, Sostril) bid or placebo was evaluated in 32 healthy volunteers undergoing upper gastrointestinal endoscopy. Drugs were taken during a period of 7 days. Endoscopic controls were performed at entry and repeated after 7 days of treatment. A damaging score was used to asses the lesions. At entry both groups showed comparable mucosal damages. The median values under ibuprofen/placebo were 1 (range 0-1) and under ibuprofen/ranitidine 1 (range 0-2). After 7 days of treatment the median lesions score increased under ibuprofen/placebo to 8 (range 1-20) whereas corresponding values in the ibuprofen/ranitidine group were constant at 1 (range 1-9). The differences between both groups were statistically significant (p < 0.05). Our data underline the protective effect of ranitidine 150 mg bid against ibuprofen both on the stomach as well as on the duodenum.

Adolescent↗
PubMed1995

[Protective effect of omeprazole against low-dose acetylsalicylic acid. Endoscopic controlled double-blind study in healthy subjects].

Protective Effects of Omeprazole against Low-dose Acetylsalicylic Acid/An endoscopic controlled double-blind study in healthy volunteers. In a randomized double-blind parallel study the gastroduodenal tolerability of 300 mg acetylsalicylic acid (CAS 50-78-2, ASA) daily (8 p.m.) has been evaluated in the presence of 20 mg and 40 mg omeprazole (CAS 73590-58-6) daily (8 p.m.) or placebo in 36 healthy volunteers using upper GI-endoscopy. The treatment periods lasted 14 days. Endoscopic controls were performed at entry and repeated at day 14. At entry the mean endoscopic score averaged 0.9 +/- 0.08 in the ASA/placebo (n = 12), the ASA/omeprazole 20 mg (n = 12) and the ASA/omeprazole 40 mg group (n = 12). The median values were 1.0. In the placebo experiments 300 mg ASA daily induced marked gastroduodenal lesions at day 14 (12.4 +/- 1.7). The median value was 10.0. Concomitant administration of 20 mg omeprazole daily afforded significant protection against 300 mg ASA daily on day 14 (2.9 +/- 0.9) (p < 0.0005 vs. ASA/placebo). 300 mg ASA + 40 mg omeprazole daily reduced the damaging score to 1.8 +/- 0.5 (p < 0.00002 vs. ASA/placebo). The median values in the ASA/omeprazole 20 mg and in the ASA/omeprazole 40 mg group were 1.0. The difference in the damaging score between ASA/omeprazole 20 mg and ASA/omeprazole 40 mg after 14 days did not reach statistical significance. Our data suggest that coadministration of 20 mg omeprazole daily reduces almost completely gastroduodenal lesions evoked by 300 mg ASA.

Adult↗
PubMed1995

[Factors affecting the results of in vitro fertilization. V. Co-culture of embryos].

Pronuclear stage embryos were divided into two groups and cultivated in i) M-199 or in ii) M-199 on a monolayer of Vero cells for 48, 60 or 72 hours respectively. Under the standard conditions (i) no significant differences in pregnancy rate (PR) were found (48 and 60 h; PR 20.14% and 20.39%). The prolonged culture influenced negatively embryo development (data not shown). On the other hand, clear differences were found after the culture on the Vero cell monolayer. Embryos cultured for 48 h gave considerably higher PR compared for 60 h (24.34% and 13.04% resp.). The embryos developing successfully after 72 h produced the highest PR (33.33%). The implantation rate is also significantly higher (19.1% P < 0.001). Although it is quite clear that our culture conditions are not yet ideal, it is evident that embryos which are able to develop normally for three days in vitro are much better equipped for further development.

Animals↗
PubMed1995

[Cryopreservation of embryos in the IVF/ET program at the Maternal and Child Care Institute in Prague].

Two methods for embryo cryopreservation using 1,2-propanediol were compared--ultra-rapid vitrification and controlled freezing. No significant differences were found in the pregnancy and implantation rates although better results were achieved by the controlled freezing method. Significantly better results both in pregnancy and implantation rates were obtained when the embryos were frozen in the pronuclear stage compared to cleaved stage embryos. In the group of pronuclear stage embryos 3 pregnancies were achieved as a result of 11 embryo transfers (27%, implantation rate 9%) vs 14 pregnancies from 193 embryo transfers (7%, implantation rate 2.5%) for the cleaved embryos.

Cryopreservation↗
PubMed1995

[Factors affecting the results of in vitro fertilization--III. The effect of the height and properties of the endometrium in the ultrasound image on the probability of implantation].

Ultrasound examination of endometrium thickness and texture (triple-line, homogenous, hyperechogenic) did not help us to predict the implantation after embryo transfer. However, in patients stimulated with GnRH analogues and hMG the endometrium was significantly higher than in patients stimulated with clomiphene citrate and hMG. Triple-line endometrium was more common in women stimulated with GnRH analogues and hMG than in those stimulated with clomiphene citrate and hMG.

Clomiphene↗
PubMed1995

[Laser-induced thermotherapy of liver metastases with MRI control. Prospective results of an optimized therapy procedure].

In a prospective study MR-guided laser-induced thermotherapy (LITT) of liver metastases was optimized and the clinical parameters evaluated. Seventeen patients (4 women, 13 men) with a total of 29 lesions underwent LITT in 25 sessions through 1 March 1994. Twelve of them suffered from colorectal carcinomas, 5 from other primary tumors. Under local anesthesia a maximum of 5 lesions per patient were treated. For MR-guided LITT a neodymium yttrium aluminum garnet laser (Nd-YAG 1064 nm) with energy varying from 3 to 7.5 W was used. Energy and application time were defined through a computer program; they varied, dependent on the lesion size, location and consistency. To monitor the progress of LITT two special thermosensitive MR sequences (Thermo-Turbo-FLASH and FLASH-2D sequences) were individually optimized, whereby the increase in temperature correlates with an increase in signal loss. All procedures were well tolerated without significant early or late side effects. In only one patient was minimal air documentated in the pleural cavity with spontaneous resorption. Patients were dismissed without complaints after 24-h hospitalization. The control parameters of the contrast-enhanced dynamic MRI documented at optimal response a hypointense signal around the tip of the laser applicator, in accordance with laser-induced necrosis. In lesions 20 mm or smaller, nearly 100% tumor necrosis was achieved and in lesions larger than 20 mm, only 50%. Follow-up evaluation 6 months after treatment shows a significantly better response in lesions with a diameter of 20 mm or smaller, with a local tumor control rate of 66%. In lesions larger than 20 mm only a local tumor control rate of 35% could be achieved. Laser-induced thermotherapy (LITT) represents a new, minimally invasive technique for tumor destruction and a high response rate in small liver metastases.

Adult↗
PubMed1995

[Factors affecting the results of in vitro fertilization--IV. Importance of the stimulation protocols combining GnRH analogs and HMG in women with unsuccessful stimulation with combinations of clomiphene citrate-HMG].

Poor responders, whose cycles were cancelled after CC-hMG stimulation because of inadequate response, were stimulated with GnRH analogues (Suprefact nasal spray) and hMG in short protocol. In this highly negative selected group the cancellation rate was significantly lower (16.2%) than in the "normal" IVF population stimulated with clomiphene citrate and hMG (24.8%). All other parameters (number of oocytes and embryos, pregnancy rate) did not differ in the two groups. Embryos were frozen in 23.4% of cycles after GnRH-hMG stimulation and in 26.1% of cycles after CC-hMG stimulation. In GnRH-a cycles more ampoules (17.7) were injected per patient than after CC-hMG protocols (11.1 ampoules). Severe ovarian hyperstimulation syndrome developed in 4.0% CC-hMG cycles and in 2.8% cycles where GnRH analogues were used.

Buserelin↗
PubMed1994

Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves predictions of RNA folding.

An RNA model system consisting of an oligomer binding to a 4-nt overhang at the 5' end of a hairpin stem provides thermodynamic parameters for helix-helix interfaces. In a sequence-dependent manner, oligomers bind up to 1000-fold more tightly adjacent to the hairpin stem than predicted for binding to a free tetramer at 37 degrees C. For the interface (/) in [formula: see text] additional free energy change, delta delta G 37 degrees, for binding is roughly the nearest-neighbor delta G 37 degrees for propagation of an uninterrupted helix of equivalent sequence, CGGC. When X and Z are omitted, the delta delta 37 degrees is even more favorable by approximately 1 kcal/mol (1 cal = 4.184J). On average, predictions of 11 RNA secondary structures improve from 67 to 74% accuracy by inclusion of similar stacking contributions.

Animals↗
PubMed1994

Protein-dependent translocation of aminophospholipids and asymmetric transbilayer distribution of phospholipids in the plasma membrane of ram sperm cells.

We have investigated the transbilayer movement of phospholipids in the plasma membrane of ram sperm cells using spin- and fluorescence-labeled lipid analogues. After incorporation into the outer leaflet, phosphatidylcholine (PC) and sphingomyelin (SM) moved slowly to the inner cytoplasmic leaflet, whereas phosphatidylserine (PS) and phosphatidylethanolamine (PE) rapidly disappeared from the exoplasmic monolayer. Variation of the initial velocity of the relocation kinetics vs the amount of analogue incorporated into the membrane suggests a saturability of the transbilayer movement of aminophospholipids. ATP depletion or pretreatment with N-ethylmaleimide of ram sperm cells reduced the fast inward motion of PS and PE, indicating a protein-mediated aminophospholipid translocation. The results suggest for the plasma membrane of ram sperm cells the presence of an aminophospholipid translocase and an asymmetric transversal lipid distribution with aminophospholipids preferentially located in the inner leaflet and choline-containing phospholipids in the outer leaflet. The relevance of the transversal segregation of phospholipids for membrane fusion processes occurring during fertilization is discussed.

Adenosine Triphosphate↗