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Biomedical subjects

E Werner

Publications and source records attributed to E Werner.

At least 19 recordsLinked to original sources

Homologies between the contiguous and fragmented rRNAs of the two Plasmodium falciparum extrachromosomal DNAs are limited to core sequences.

Plasmodium falciparum contains two extrachromosomal DNAs, a 6 kb linear element and a 35 kb circular DNA; both encode rDNA sequences. The 6 kb element rDNAs comprise fragments of both large and small subunit rRNAs. Comparison of these with corresponding rDNA sequences from the 35 kb DNA and E. coli show that sequences conserved between the three are largely confined to highly conserved core regions; in fact, most of the 6 kb rDNA sequences correspond to core regions. Both the 6 kb element and 35 kb rDNAs show less conservation to each other than to E. coli sequences, suggesting that the two extrachromosomal DNAs of P. falciparum are not closely related. The characteristics of the fragmented rRNAs from the 6 kb element suggest they are functional, possibly in mitochondrial ribosomes.

Animals

Measurement of iron bioavailability by means of stable 54Fe and mass spectrometry.

Stable isotopes represent a useful tool for the assessment of biokinetic parameters in in vivo studies on humans. A procedure is described to evaluate the bioavailability of iron in pharmaceutical preparations by means of 54Fe as a tracer and mass spectrometry for the determination of time dependent changes in the isotope ratio of 54Fe/56Fe in red blood cells. Iron tablets with an increased portion of 54Fe were administered to iron deficient subjects and red cell iron utilization was used as a measure of iron bioavailability. Iron utilization was derived from changes in the 54Fe/56Fe ratio as evaluated by means of fast atom bombardment-mass spectrometry (FAB-MS) on processed blood samples. A good intraindividual reproducibility was observed for blood samples drawn at various times after application of the trial drug. Figures for bioavailability and its interindividual variations were in the range expected from comparable studies on similar iron preparations using radioiron as tracers. The results obtained show that quantitative data of bioavailability from pharmaceutical iron preparations may be obtained without radiation exposure of the subjects investigated.

Administration, Oral

Changes of erythropoietic and storage iron components in certain clinical situations as evaluated by ferrokinetic investigations.

A method is described for the quantitative analysis of in vivo organ measurements of 59Fe activity in ferrokinetic investigations. The time-activity curves obtained by sequential surface monitoring over sacrum, liver and spleen can be resolved quantitatively into their different components contributing to the recorded count rate. The analysis is performed in three steps: (1) Count rate contributions from activity in other organs and from scattered radiation from regions outside the organ under investigation are corrected. (2) Distinction is made between radioactivity uptake of the tissue and radioactivity contained in the perfusing blood. (3) The resulting net organ activity is then further resolved into an erythropoietic and a storage iron component by use of a computer program (SAAM-27) and assuming a compartmental model for internal iron exchange. The method was tested in three groups of patients with different haematological disorders and in normal controls. Characteristic patterns of the parameters are found for different diseases and the results correlated well with the clinical findings. It is concluded that in vivo organ measurements of 59Fe activity, when performed and analysed with sufficient care, can provide an insight into the dynamics of the iron exchange that is taking place in an organ. This analytical approach may improve the diagnostic predictions of ferrokinetic investigations.

Erythropoietin

T-cell-dependent immunity and thrombocytopenia in rats infected with Plasmodium chabaudi.

Normal, splenectomized, and athymic Fischer rats were infected with Plasmodium chabaudi. In normal rat infections, acute-phase infection resolved rapidly and completely. In splenectomized rats, infection resulted in high parasitemia and ultimately death. In nude rats, parasite growth was reduced compared with normal rats, and a persistent parasitemia (between 20 and 45%) was observed for several months. Complete resolution of the infection was achieved after adoptive transfer of T lymphocytes, even when transfer occurred during the course of infection. These results indicated that an acquired, T-lymphocyte-dependent immunity was necessary for the complete recovery observed in normal rats. In normal rats, thrombocytopenia and splenomegaly occurred during infection. By contrast, in nude rats, both of these pathological manifestations were only observed after thymus grafting. Thrombocytopenia was also absent in the splenectomized animals. Despite an increase in platelet-associated immunoglobulin levels during the infection, thrombocytopenia was not transferred by injection of infected rat serum to normal recipients. It has been concluded that the nude rat infection can be regarded as a novel and useful model for studying the T-cell-dependent effector and pathological mechanisms and to investigate the anti-P. chabaudi immune response.

Animals

Effect of recombinant human erythropoietin on iron balance in maintenance hemodialysis: theoretical considerations, clinical experience and consequences.

Iron deficiency is the main reason for insufficient response to rEPO therapy. Serum ferritin and transferrin saturation give valuable information on storage iron and iron transport. Iron demand for correction of anemia can easily be estimated after HCT (vol%) x average blood volume (dl) = mg iron. Inadequate iron supply of the bone marrow in the presence of sufficient storage iron in the RES develops frequently under rEPO, possibly explaining the improvement of bone marrow response to rEPO by concomitant intravenous iron supply. The reasons of functional iron deficiency are still speculative.

Anemia

Tattooing and high-risk behaviour among drug addicts.

One hundred and seventy-five patients treated at the drug dependence outpatient ward of the Psychiatric University Clinic of Vienna were investigated in February 1990 using a standardized questionnaire which included questions concerning tattoo behaviour. The tattooing procedure, often carried out in prison and employing unsterile equipment, is a possible way of HIV-1 transmission. It is recommended that the fragmentary legislation in Austria be rewritten and made more effective. According to a ministerial order only medical doctors are allowed to procure a licence for tattooing as it is an invasive procedure. Therefore no licensed tattooing establishments controlled by public health offices exist. Their legal existence would guarantee a hygienic standard and reduce the danger of infection.

Acquired Immunodeficiency Syndrome

Stable isotopes for determining biokinetic parameters of tellurium in rabbits.

We have compared the use of stable and radioactive isotopes for determining the concentration of tellurium in body fluids of animals and man, specifically in the blood plasma of rabbits. Particular effort has been devoted to developing a sample-processing technique that allows the total amount of tellurium and isotope ratios to be measured by graphite furnace atomic absorption spectrometry (GFAAS) and secondary ion mass spectrometry (SIMS), respectively. The procedure employed in the SIMS analysis is discussed in detail. Investigations on the plasma clearance and the fractional intestinal absorption were carried out on four rabbits. Tracer solutions containing stable tellurium enriched in 124Te or 126Te and radioactive tellurium (121mTe or 123mTe) were administered by gavage and/or intravenously. Blood samples were drawn during the first 2 days after application. The activity of the separated plasma was measured by standard gamma ray spectrometry. After wet ashing and solvent extraction with MIBK the samples were analyzed for stable tellurium. A detection limit of 1 ng/mL of plasma could be achieved with GFAAS. For SIMS analysis the processed samples were deposited on high-purity graphite backings. Reliable isotope ratios could be determined with sample fractions containing 1 ng of tellurium or even less. The results obtained by applying stable isotopes were found to be in good agreement with the data achieved by using radioactive tracers. Studies on the intestinal absorption and the metabolic behavior of tellurium in human volunteers may thus be performed with stable isotopes.

Animals

Optimized conditions for electrotransformation of bacteria are related to the extent of electropermeabilization.

Electropulsation is a simple and efficient way to introduce cloned genes into a variety of cell types, even with walled species. In the case of bacteria, we observed no direct correlation between survival rate and transformation yield. In the present work, we show that the yield of transformation is directly related to the level of the electric-field induced level of cell permeabilization. From experiments on Escherichia coli, it was confirmed that the extent of associated ATP leakage was a reliable assay. This approach was extended to other strains, such as Salmonella typhimurium, which to date had not been electrotransformed by plasmids.

Adenosine Triphosphate

Sharing spoons: a risk factor for HIV-1 infection in Vienna.

Sharing of needles and syringes plays a central role in HIV-1 transmission among intravenous drug users (IVDUs). There have been several suggestions to protect the injecting population from further harm, but focused mainly on the use of sterile needles and syringes as well as information about safer sexual behavior. This study examined a total of 366 IVDUs at the drug dependence out-patient ward of the Psychiatric University Clinic of Vienna. HIV-1 antibodies were found in 29.7% (58) in 1989 and in 26.9% (42) in 1990. The results show that in 1989 14% and in 1990 5% IVDUs who never shared needles or syringes or other drug paraphernalia were found to be HIV-1 positive. In spite of the high information standard among Viennese drug addicts on risk reduction, the underestimated co-factors during drug administration might be responsible for a further HIV-1 transmission. Educational interventions on this subject should address even IVDUs who do not share needles and have adjusted to 'safer sex' practices.

Austria

Assessment of iron availability using stable 54Fe.

This paper describes a method of quantitatively assaying the bioavailability of orally administered iron in order to promote haemoglobin synthesis in iron deficiency anaemia. The non-radioactive tracer substance 54Fe was employed. An experimental iron deficiency model was tested in 18 healthy male volunteers. The trial design made it possible to assess intestinal absorption and efficacy of iron substitution. The iron deficiency was experimentally induced by weekly phlebotomy. Two commercially available iron preparations with different rates of iron release were investigated at a dosage of 150 and 160 mg Fe2+ daily, respectively. In the first seven days of treatment, both preparations were administered in 54Fe-labelled form. Afterwards, iron substitution was given with the commercially available preparations. Measurements were made of erythrocyte utilization of 54Fe and plasma iron tolerance curves at the beginning of the periods in which the 54Fe-labelled product and the commercially available preparation were administered, and of haemoglobin and serum ferritin concentration curves over three months. The mean utilization of the iron administered was virtually identical for the two preparations (23 and 22%, respectively). Likewise, there was no difference with respect to the average daily increase in haemoglobin concentration in the blood (1.5 g 1-1). There was also no significant difference with respect to serum ferritin concentration curves. In contrast, the two preparations differed markedly with respect to the plasma iron tolerance curves. This suggests that evaluation of plasma iron tolerance curves alone is not suitable for comparative assessment of the therapeutic value of orally administered iron preparations.

Administration, Oral

A greater than 200 kb deletion removing the entire beta-like globin gene cluster in a family of Irish descent.

We describe a new deletional form of gamma delta beta-thalassemia segregating in two generations of a family of Irish descent. Affected family members present with a beta-thalassemia minor phenotype, normal Hb A2 and Hb F levels. Genomic blotting analyses on DNA from affected family members show heterozygosity for a large deletion beginning at least 15 kb upstream of the 5' endpoint of the gamma delta beta-thalassemia-1 deletion, extending through the entire beta-like globin gene cluster, and continuing for at least 10 kb beyond the 3' endpoint of the deletion associated with the Spanish form of delta beta 0-thalassemia. This deletion is among the largest described so far, and removes at least 205 kb encompassing the entire beta-like globin gene cluster on chromosome 11.

Adult

[Circadian rhythm of the toxicokinetics and toxicodynamics of the plant protection substance dinitro-ortho-cresol in rabbits].

Results from chronotoxicological investigations with the plant protection chemical DNOC has been described and judged. It has been studied hyperthermia caused by i.v. application of 7.5 mg/kg body weight on rabbits to 6 different times, starting at 4 a.m. with 4-hours-intervals as well as the dose-effect relation in each case with 3 doses to the time of application at 12 a.m., 6 p.m., 12 p.m. and 6 a.m. and the renal DNOC excretion after a dose of 10 mg/kg body weight. There was found a time dependent rhythm in all experiments. Acrophase of hyperthermia is placed in the middle of the phase of activity of the animals at 12 p.m., however it depends on the dose. The results are showing, that the position of acrophase by constant environmental factor is neither a substance specific nor an animal specific constant.

Animals

[Nicotine--drug addiction--AIDS. Drug use habits of Vienna addicts].

In Austria it is illegal to sell tobacco to young adolescents. A diverse sample of 358 narcotic addicts was investigated at the Psychiatric University Clinic of Vienna. Data were obtained from on site confidential interviews and a HIV-test was conducted. The individual drug use history was recorded and, interestingly, tobacco addiction was the first stage in starting a drug career. Furthermore, a strong correlation was observed between onset of heroin use and HIV-1 infection. It is concluded that in Austria not only the availability nicotine and alcohol to young adolescents should be prohibited, but also their use should be punishable. Easy access to nicotine as in public restaurants or from automatic distributors, has to be withdrawn. Tobacco advertisements may drive vulnerable young adolescents to early nicotine abuse and this may be followed by addition to other drugs and diseases causing death, including AIDS. Socioeconomic data, as well as the methadone data are presented. 180 out of the 358 patients were on methadone maintenance. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society. Physicians have a clear responsibility to lead the effort on all fronts against tobacco, especially in view of the HIV epidemic.

Adolescent

Renal excretion of tellurium after peroral administration of tellurium in different forms to healthy human volunteers.

As tellurium ranks among the rare non-essential trace elements there is only little known of its intestinal absorption and its metabolic behaviour in humans. Data for risk evaluations needed for occupational medicine are based on animal experiments only. In order to investigate the metabolic behaviour of tellurium in man, tellurium in different forms was administered perorally to healthy male human volunteers. It was given as sodium tellurate, sodium tellurite, metallic colloid and intrinsically bound in cress. For the latter, cress was cultivated with tellurium-containing water in order to provide tellurium for ingestion in a form which is more equivalent to foodstuffs. After the administration the urinary excretion of tellurium was determined. Tellurium concentrations were measured in urine samples by means of graphite furnace atomic absorption spectroscopy (GFAAS) after wet ashing and a preconcentration of tellurium by solvent extraction with isobutyl methyl ketone (IBMK). From the cumulative tellurium excretion in the first four days after the administration, a percentage intestinal absorption of 25% +/- 10% for soluble tellurium salts can be calculated. The renal tellurium excretion is faster after administration of hexavalent tellurium than after ingestion of the tetravalent form. This can explain the higher toxicity of the tetravalent tellurium compounds found in animal experiments. The introduction of tellurium to cress lowered the intestinal absorption to approximately 15%. For metallic tellurium the fractional intestinal absorption was found to be about 10%.

Adult

[A phagocytosis test for the evaluation of the local immunity status during endometritis therapy with special regard to the use of uterofertil in cattle].

After the influence of organic acids or peroxide acids with low concentration upon mucous membranes results a higher activity of the topical defence-situation. The application of a 0.2 per cent solution of peroxyethane acid (drug Uterofertil) into the uterus for endometritis-therapy directs an increase of phagocytosis-activity not only topical but also in the peripheric circulation of blood. The phagocytosis-activity was measured with a test by granulocytes. Other drugs were also tested, which will needed by endometritis-treatment of cattle.

Animals