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Biomedical subjects

R Strobel

Publications and source records attributed to R Strobel.

At least 19 recordsLinked to original sources

A new UHV angle encoder for high-resolution synchrotron radiation monochromators.

The high precision of 0.1 arcsec required for the positioning of optical elements in new two-axes monochromators at the undulator beamlines at BESSY II has led to the development of UHV-compatible high-precision angle encoders. Mounted directly on the rotation axes, they provide substantial advantages over measuring systems connected outside the vacuum vessel. Making use of a fast closed-loop control system, an accuracy of 0.1 arcsec at a resolution of less than 0.01 arcsec has been experimentally verified.

Journal Article↗

[Preoperative diagnosis with stereotactic biopsy is a good predictor of breast cancer in radiologically non-benign breast lesions].

OBJECTIVE: To evaluate histological needle biopsy in breast lesions classified radiologically as 'non-benign'. DESIGN: Prospective, descriptive. SETTING: Hospital Velp, Velp, the Netherlands. METHODS: 232 women with an 'uncertain', 'suspicious' or 'malignant' result of mammography, if necessary supplemented by echography, were subjected to histological biopsy from a breast between 1 January 1994 and 1 January 1997. The earlier biopsies were made with a 16 Gauge (G) needle, those after April 1996 with a 14 G needle, as a rule under stereotactic control. In principle, operation was performed after a positive result. Concerning the women operated after the biopsy, the results of the histological examinations were compared in a 2 x 2 table. RESULTS: 165 of the 232 patients (71%) had breast cancer. Of the 59 patients classified roentgenologically as 'uncertain', 15 (25%) had breast cancer, of the 'suspicious' cases this ratio was 44/67 (66%) and of the 'malignant' results it was 106/106 (100%). Operation was performed in 186 women. The biopsy findings and the surgical preparation were in agreement in 169 patients (91%). The sensitivity of the stereotactic biopsy was 90%, its specificity 93%. One woman was over-treated (axillary lymph node resection) because of a biopsy classified as malignant performed on a rare tumour ultimately diagnosed as 'adenomyo-epithelioma with epithelial atypia'. The proportion of false-negative results was 36%. The predictive value of a positive result was 99%, that of a negative result 63%. CONCLUSION: A diagnostic stereotactic biopsy after roentgenological classification based on mammography and echography had a good predictive value regarding the probability of breast cancer.

Biopsy, Needle↗

Joint NASA-ESA-DARA Study. Part three: characterization of sleep under ambient CO2-levels of 0.7% and 1.2%.

An experiment was conducted to study sleep quality and sleep architecture in volunteers living in a closed system under elevated ambient CO2 levels of 0.7% and 1.2%. In a closed system, human life is possible only if the CO2 level is permanently adjusted. For the Russian space station MIR, for example, the CO2 levels of the present study are actual upper limits for the adjustment. Sleep architecture was found to be altered in astronauts on the orbiting MIR station. Sleep quantity and quality were reduced. The latency to the first REM sleep was shorter in space and slow wave sleep was redistributed from the first to the second sleep cycle. The elevated CO2 concentration in the atmosphere on MIR may be one of the reasons for those observations regarding sleep in space. Thus, this experiment was also conducted in order to clarify the interpretation of data obtained from astronauts on MIR. In this study sleep polygraphies could be recorded in 4 subjects who lived for 23 d under 0.7% and then for the same period of time under 1.2% CO2. Findings suggest that these levels of ambient CO2 do not reduce sleep quality. Sleep architecture, however, was slightly changed and showed that the amount of slow wave sleep increased with the duration of the exposure to CO2. But it can be excluded that findings on MIR were caused by elevated CO2-levels.

Adult↗

Replication and extension of a risk profile for Amerasian youth.

The relationship between number of risk factors and symptoms of anxiety and depression was examined in a cohort of Vietnamese Amerasians, replicating a study done with a previous cohort. One hundred forty seven subjects awaiting U.S. placement completed the Hopkins Symptom Checklist, the Vietnamese Depression Scale, and a questionnaire which included items found to be risk factors for psychological distress among Amerasians. Number of risk factors was linearly related to symptoms of both depression and anxiety. Results are consistent with previous findings of the relationship between risk factors and symptoms of psychological distress. The profile may be helpful in anticipating which refugees may be at risk for future psychological distress, and thus be useful in preventively allocating scarce treatment resources.

Adolescent↗

Aneurysm formation in modified human umbilical vein grafts.

OBJECTIVES: Aneurysm formation in Human Umbilical Vein Grafts has been reported to be as high as 65% after 5 years. One of the causes might be the structure of the Biograft-wall and in 1985 a new method of processing the graft was begun. In Groningen this new improved Biograft has been used since late 1986. DESIGN: Duplex scanning was used to examine the frequency of aneurysm formation in the new improved Biograft. MATERIALS: Sixty-nine patent Biografts have been examined in a period up to 6 years after implantation. MAIN RESULTS: Aneurysms were found in only 17% of grafts although the frequency increased with time. Dilatation was common but may be due to a more elastic graft. CONCLUSION: These findings justify the continued use of the new Biograft as a substitute for arterial femoropopliteal reconstructions.

Aged↗

Genotoxicity of 17 gyrase- and four mammalian topoisomerase II-poisons in prokaryotic and eukaryotic test systems.

The genotoxic potency of certain classes of topoisomerase II poisons is correlated with their affinity to the topoisomerase protein rather than with the presence of 'classical' structural alerts for DNA reactivity: bacterial topoisomerase II poisons (specifically named gyrase inhibitors) are highly genotoxic in prokaryotic systems; mammalian topoisomerase II poisons are potent mutagens/clastogens in eukaryotic systems. Studies with bacterial, lower eukaryotic and mammalian genotoxicity tests were performed to draw structure-activity conclusions and address risk-benefit considerations for the class of quinolone gyrase inhibitors. All 17 gyrase inhibitors investigated in this study showed genotoxic activity in Salmonella typhimurium strain TA102 and the SOS test. The genotoxic and the toxic activities increased in a highly parallel fashion from the parent compounds, nalidixic acid and oxolinic acid, to the new generation fluoroquinolones. Generally, the most potent fluoroquinolones also show clear-cut positive effects in eukaryotic test systems, although at concentrations 100-1000-fold higher than those effective in bacteria and also 100-1000-fold higher than the minimal genotoxic concentrations of antitumour topoisomerase II inhibitors (ellipticine, teniposide, mAMSA) used as reference compounds. However, subtle structural modifications of the quinolones can strongly diminish the preferential genotoxicity in the prokaryotic test systems.

Animals↗

Photomutagenesis test development: I. 8-Methoxypsoralen, chlorpromazine and sunscreen compounds in bacterial and yeast assays.

Two in vitro genotoxicity tests have been adapted to the evaluation of photomutagenic activity of test compounds. The study was initiated to obtain an experimental basis relating to newly proposed guidelines of the EC which request the screening of UV-absorbing compounds, for example, those employed in sunscreen preparations, for their photomutagenic potential. The well established photomutagens 8-methoxypsoralen and chlorpromazine were used to define relevant test protocols. The compounds were evaluated with the Ames test and the Saccharomyces cerevisiae D7 test for gene conversion. The influence of various parameters such as UV light sources, spectral composition, UV sensitivity of the test systems, absorbance by test materials and different exposure conditions is indicated. Two exemplary screening experiments with cosmetic ingredients are presented. Both test systems can be employed for the evaluation of compounds for photomutagenic activity although the standard excision-deficient strains of S. typhimurium pose problems because of their high UV sensitivity. The present experience in this complex field suggests that rigid test protocols and a restrictive test battery would be inadequate.

Chlorpromazine↗

Ion channel enzyme in an oscillating electric field.

To explain the electrical activation of several membrane ATPases, an electroconformational coupling (ECC) model has previously been proposed. The model explained many features of experimental data but failed to reproduce a window of the field intensity for the stimulated activity. It is shown here that if the affinities of the ion for the two conformational states of the transporter (one with binding site on the left side and the other on the right side of the membrane) are dependent on the electric field, the field-dependent transport can exhibit the observed window. The transporter may be described as a channel enzyme which opens to one side of the membrane at a time. It retains the energy-transducing ability of the earlier ECC models. Analysis of the channel enzyme in terms of the Michaelis-Menten kinetics has been done. The model reproduced the amplitude window for the electric field-induced cation pumping by (Na,K)-ATPase.

Adenosine Triphosphatases↗

Toxicological investigations with the benzodiazepine antagonist flumazenil.

The benzodiazepine antagonist ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate (flumazenil, Ro 15-1788, Anexate) was investigated in a series of toxicological studies. In a single intravenous injection study in male and female mice and rats, the highest non-lethal (maximum tolerated) doses were found to be between 62.5 and 125 mg/kg (the amounts of flumazenil present in the aqueous ampoules available for intravenous injection in man are 0.5 and 1.0 mg). In intravenous studies of 4 weeks duration, 10 mg/kg/d were systemically well tolerated in dogs and rats. In 13-week oral studies, 80 mg/kg/d were very well tolerated in dogs (capsule administration) and, after 125 mg/kg/d (by feed-admix) in rats, no untoward compound-related findings apart from a 10-15% increase of the liver weights in females were made. In reproductive toxicity studies, flumazenil revealed no drug-related embryotoxic or teratogenic effect and no adverse effects upon fertility of dosed animals themselves or on the peri- and postnatal development of their offspring. There was no indication for mutagenic potential of flumazenil in vitro concerning induction of gene mutations or clastogenic effects. An in vivo DNA repair test using germ cells of male mice did not yield DNA-damaging activities. From all these toxicological investigations it can be concluded that the risk in man given therapeutic doses or even intentional or accidental overdoses of flumazenil is extremely small.

Administration, Oral↗

Criteria for the standardization of Salmonella mutagenicity tests: results of a collaborative study. II. Studies to investigate the effect of bacterial liquid culture preparation conditions on Salmonella mutagenicity test results.

The influence of various parameters and growth conditions in the "overnight culture" of Salmonella typhimurium strains on mutagenicity test results was investigated. A number of factors were first suspected to be of some importance for the quantitative outcome of the mutagenicity test. None of them, however, was found to influence the results to such a marked extent as to be a major source of variability. Only the brand of nutrient broth used for the propagation of the bacteria proved finally to have a certain effect on the number of (spontaneous and induced) revertant colonies, although no precise and quantitative statements can be made with regard to a possible standardization of this experimental segment in the Salmonella mutagenicity test. The occurrence of such unpredictable but noticeable influences is, however, evidence for the importance of an intralaboratory optimization and standardization of all parts of the test procedure.

Animals↗

Reproducibility of and experiences with the BHK cell transformation assay.

Transformation of BHK 21 C 13 cells was investigated using the ability of transformed cells to reproduce in semi solid agar (anchorage independent growth). A number of modifications to previously published methods have been made, our assays were carried out on 16 compounds, including both carcinogens and non-carcinogens as judged by in vivo bioassay. Reproducibility of test results within the laboratory and with data derived from literature could be shown. Experiences concerning the optimal growth of transformed cells and the threshold level to differentiate between positive and negative results are discussed.

Animals↗