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Biomedical subjects

H Eggers

Publications and source records attributed to H Eggers.

At least 19 recordsLinked to original sources

Chemical stability, biological activity and cellular uptake of a cisplatin analogue having a 1,2-diarylethyleneamine ligand in cultures of human breast cancer cells.

The platinum(II) complex PtCl2(meso-6), which has the estrogenic ligand meso-1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine (meso-6), has been reported to be an effective antitumor drug for estrogen-receptor(ER)-positive tumors in animal experiments. The goal of this study was to investigate whether the observed biological effects could be ascribed to the intact PtCl2(meso-6). Cultures of the ER-positive human breast cancer cell line MCF-7 were used as the in vitro test system. In culture medium containing 10% fetal calf serum, PtCl2(meso-6) had a half-life of about 2 h, as determined by HPLC analysis, and no PtCl2(meso-6) was detectable after 10 h. The Pt complex bound irreversibly to serum protein. After 30 min, the diamine ligand was found released, with a maximum conversion of about 35% at 24 h. At this time the culture medium still had estrogenic activity, i.e. it induced ER processing in the MCF-7 cells. This indicates that the estrogenic effect was elicited by the released diamine ligand. In contrast, the growth-inhibitory activity of the medium preincubated with PtCl2(meso-6) was lost at a rate similar to the rate of loss of PtCl2(meso-6) from the medium. This accords with the platinum complex being the main cytotoxic entity. When MCF-7 cells were incubated with PtCl2([3H]meso-6), no free Pt complex could be identified in cellular extracts, and most of the cell-associated radioactivity coeluted with meso-6 in HPLC analysis. After 12 h, only 1.4% of the total cellular platinum was bound to DNA, but no tritium label could be detected. In conclusion, diamine ligand is released from the Pt(II) complex and can account for the estrogenic effects so far ascribed to PtCl2(meso-6).

Antineoplastic Agents

Neonatal lensectomy and intraocular lens implantation: effects in rhesus monkeys.

PURPOSE: To compare the effects of a lensectomy with and without intraocular lens (IOL) implantation on a neonatal rhesus monkey eye. METHODS: A lensectomy and anterior vitrectomy was performed on 75 monkeys during the first 16 days of life; 21 of these monkeys also had an IOL implanted into the posterior chamber. The eyes were examined at regular intervals using biomicroscopy, applanation tonometry, and ophthalmoscopy. RESULTS: The pseudophakic monkeys were studied until they were 92.5 +/- 5.8 weeks of age and the aphakic monkeys until they were 80.4 +/- 5.7 weeks of age. Pupillary membranes (100% versus 55.5%; P < 0.01) and lens regeneration into the pupillary aperture (28.6% versus 5.6%; P = 0.02) occurred more often in the pseudophakic than the aphakic eyes. As a result, the pseudophakic eyes required more reoperations than the aphakic eyes to keep the visual axis clear (P < 0.01). There was not a significant difference in the incidence of ocular hypertension between the pseudophakic and aphakic eyes (9.5% versus 12.7%; P = 0.34). Pupillary capture of the IOL optic occurred in 52% and haptic breakage in 33% of the pseudophakic eyes. All of the eyes with broken haptics had a prominent Soemmerring's ring varying in maximum thickness from 0.6 to 2 mm. Nine of the haptics from the seven eyes with broken IOLs had eroded into the iris, two into the ciliary body, and one into the anterior chamber. CONCLUSIONS: Implanting an IOL into a neonatal monkey eye after a lensectomy and anterior vitrectomy increases the likelihood of a reoperation being necessary. Haptics frequently erode into the iris and ciliary body and may break because of stress placed on the optic-haptic junction by forward movement of the IOL.

Animals

Cimetidine alters the disposition kinetics of the monoamine oxidase-A inhibitor moclobemide.

The influence of cimetidine on the absorption and disposition of moclobemide was examined in eight healthy male subjects. A single 100 mg intravenous and 100 mg oral dose of moclobemide was administered before and after 2 weeks of cimetidine administration (200 mg five times a day). The data on intravenous administration indicated that cimetidine produced a statistically significant alteration in the following disposition parameters (mean values for control versus cimetidine): systemic clearance, 46.6 versus 28.3 L/hr; mean residence time, 2.1 versus 3.2 hours; elimination half-life, 1.6 versus 2.3 hours. There was no significant difference in the steady-state volume of distribution. The absolute oral bioavailability of moclobemide increased significantly after cimetidine administration (54% versus 68%), as did the maximum plasma concentration after a single oral dose (575 versus 787 ng/ml). There were no differences in the mean absorption time or time to achieve maximum concentration. The values of systemic and apparent oral clearances of moclobemide after cimetidine administration were directly related to the corresponding control values before cimetidine. In contrast, the percentage change in clearance was essentially independent of the corresponding initial control clearance value.

Adult

Determination of the new fluoroquinolone fleroxacin and its N-demethyl and N-oxide metabolites in plasma and urine by high-performance liquid chromatography with fluorescence detection.

A high-performance liquid chromatographic method is described for the determination of the new fluoroquinolone fleroxacin and its metabolites in plasma and urine. Plasma samples are deproteinized with acetonitrile, and, after evaporation and reconstitution of the supernatant, samples are analysed on a reversed-phase column. The limit of quantification is 10-20 ng/ml for the parent drug and 10 ng/ml for the metabolites, using a 0.2-ml sample. Urine samples are diluted with the mobile phase. An aliquot is then injected directly onto the column. The limits of quantification are 1 micrograms/ml for the parent drug and 0.5 micrograms/ml for the metabolites, using a 0.1-ml sample. The method has been successfully applied to pharmacokinetic studies of human volunteers and patients.

Anti-Infective Agents

[Birth weight of newborn infants in relation to body height and body weight of parents with special reference to duration of pregnancy].

Using the data of the 1985 GDR somatogram standards (birthweight percentiles calculated from 51,570 liveborn singletons) the impact of parental weight and length on the birthweight were calculated. Peristatic factors in combination with the genetic 'anlage' act first of all via maternal weight. Body height and/or length of mother and father are more representative for the genetic constitution. Their impact on neonatal weight seems to be less significant, however statistically calculable. The paternal 'anlage' is relatively modified by the intrauterine environment (maternal constitution).

Birth Weight

[Neonatal percentile values for the GDR--1985. Correlation of body weight and length in newborn infants (calculation of birth weight/body length in cm. with reference to gestational age)].

Taking account of the gestational age (28th to 42nd completed week of pregnancy) the sex-related ratio of birth weight to length (g/cm) for newborn infants is reported. This shows that observation of the correlation between birth weight and length with reference to gestational age makes a more accurate classification of newborn infants possible, rather than using a two dimensional classification (birth weight week of gestation).

Birth Weight

[Immunosuppressive and cytostatic effectiveness of the poplar mushroom Tricholoma populinum LANGE].

Dry powders or extracts of the fruit bodies of Tricholoma populinum given per as or injected intraperitoneally respectively caused a suppression of the number of plaque forming cells of mice as shown by the hemolysis-plaque-assay. Extracts of the fungi inhibited above that the incorporation of 3H-thymidine into mitogen-stimulated human lymphocytes as observed in the lymphocyte transformation test and retarded the proliferation of cultivated bovine aortic endothelial cells.

Animals

[Pregnancy in adolescence--psychosocial development of young mothers and their children].

Hitherto existing concepts on circumstances favouring pregnancies in adolescents have mainly focussed attention on physically precocious maturity, on social risks and on the type of personality of the pregnant adolescents. Based on our material this opinion seems to be in need of correction. Changing of the validity of these factors may be suggested due to psychosocial conditions in connection with both the acceleration of maturity and a new estimation of sexuality including heterosexual development at earlier stages of life. Children from 100 juvenile mothers were clinically and psychologically investigated at the age of 7 years. Neither serious social problems in the children nor considerable deviations of mean average of the physical, mental or social age specific standards could be observed.

Adolescent

[East German percentile values for newborn infants--1985 relation of age, parity, body weight and height of the mother and the birth weight of newborn infants].

Based on an analysis of very comprehensive data material multidimensional investigations on connections between age, parity, weight and height of mothers and birth weight of infants have been made. Maternal height as well as maternal weight have a considerable influence on birth weight of infants. At the same maternal height infant birth weight will rise in connection with the rise of maternal weight. Maternal age, parity and weight are correlated variables. The older a woman, the higher on average is not only her parity but at the same her weight, too. The rise of maternal weight per year in the statistic mean amounts to 401 g. Moreover, at the same age like primiparae second and subsequent parae are of higher weights so that partly maternal weight contains indirectly not only maternal age but also maternal parity. The following range of the influencing factors maternal height, weight, parity and age on birth weight can be given: 1. Height and weight as relatively equivalent factors, 2. parity and 3. age.

Adolescent

[New percentile values for birth weight, body length, head and breast circumference of newborn infants in East Germany].

Somatometric data of 51,570 newborns (singles) delivered between the 28th and 42th week of gestation from different, representative areas of the G.D.R., concerning birth weight, body length, head and breast circumference are presented as tables and percentile curves separately for either sex. The values are recommended as reference values for the assessment of fetal development related to gestational age in the G.D.R.

Anthropometry

[Neonatal percentile values for East Germany--1985. 3. On the correlation of body height and weight of the mother in a two-dimensional classification of newborn infants according to birth weight and gestational age].

There were published percentiles of birthweight in relation to bodyheight of the mother as well as in relation to bodyweight and parity, bodyheight and bodyweight of the mother for term range 37th to 41st week of pregnancy. They were calculated through median quantities. The dates again derive from the investigation of 51,570 single births in elected regions of GDR in 1984 and 1985. The length of pregnancy was stated in full weeks. It was determined on the base of three parameters (by Naegele method, by sonography, and by neonatal maturity judgment). Selected percentiles of birthweight regarding the above influencing factors, distributed into sex, were summarized for use in practice.

Birth Weight

[Percentiles of newborns in the DDR--1985. 1. Percentiles of birth weight and birth height].

Body measures of newborn infants and their parents were comprehended and statistically revised in 30 hospitals of German Democratic Republic in 1984-1985. There were records of 52,570 single livebirths without birth defects of women living in the GDR (51.3 per cent boys and 48.7 per cent girls). Percentiles were calculated and demonstrated in tables and figures. Base of calculation of percentiles was a pregnancy week final diagnosis. It was determined by the physician resulting from three investigations of pregnancy week (methods Naegele; ultrasound; maturity index). Percentiles of birthweight and birthlength of newborn infants in GDR in 1984-1985 are lower than those in 1973-1974. Causes are discussed. Our results are compared with two Middle European curves and with Lubchenco curve (1963).

Body Height

Effect of food intake on the relative bioavailability of moclobemide (Ro 11-1163).

Twelve healthy adult volunteers received a single 100-mg tablet of moclobemide in an open-label crossover study designed to determine the influence of food on moclobemide absorption. Moclobemide was administered 30 min after a standard breakfast as well as under fasting conditions. Moclobemide absorption was rapid in the absence of food. Bioavailability parameters obtained when drug was taken 30 min after the meal suggested that the rate of absorption was slightly decreased in the presence of food (mean Tmax 0.71 h vs. 1.14 h), while the extent of absorption of moclobemide given with food was unaltered. The decreased absorption rate in the presence of food is not expected to be of clinical significance.

Adult

Determination of the new monoamine oxidase inhibitor moclobemide and three of its metabolites in biological fluids by high-performance liquid chromatography.

A sensitive high-performance liquid chromatographic method has been developed for the determination of moclobemide and three of its metabolites in plasma and urine. The four substances and the internal standard were extracted from basified plasma (pH 11) with dichloromethane, with recoveries of generally more than 70%. A column packed with 5-microns Spherisorb hexyl phase and an eluent consisting of acetonitrile and aqueous phosphate buffer 30:320 (v/v) with a pH of 3.9 were found most suitable for the chromatographic separation of the four compounds of interest. Non-ideal interactions of the basic compounds and the N-oxide metabolite occurred with many other reversed-phase materials, as indicated by broad and tailing peaks. Limits of quantitation for moclobemide and its three metabolites in the range 20-30 ng/ml and a good intra-assay reproducibility ranging between 2 and 5% for concentrations over 100 ng/ml could be achieved for plasma, which increased to ca. 8-10% at a concentration of 50 ng/ml.

Benzamides

Disposition kinetics of moclobemide, a monoamine oxidase-A enzyme inhibitor: single and multiple dosing in normal subjects.

The absorption and disposition kinetics of moclobemide (Ro 11-1163), a new reversible and preferential monoamine oxidase-A enzyme inhibitor, were examined in 12 normal male subjects. An intravenous infusion was administered before and after a 15-day multiple oral dosing regimen (100 mg t.i.d.). Plasma concentration-time data were obtained after each intravenous infusion, after the first oral dose, during two dosing intervals at steady state, and before the second daily dose on several days. The disposition values (percent coefficient of variation in parentheses) after the first and second intravenous infusions, respectively, were: clearance, 39.4 (15%) and 29.1 (12%) L/hr; elimination half-life, 1.60 (15%) and 2.00 (18%) hours; and volume of distribution at steady state, 84.3 (11%) and 80.7 (15%) L. The absolute oral bioavailability increased from 0.56 after the first oral dose to 0.86 and 0.90 after the first and second weeks of administration, respectively. The reduced metabolic, presumably hepatic, clearance may be the result of self-inhibition or metabolite inhibition of moclobemide clearance.

Administration, Oral

Computer-assisted spectral electroretinography in vitrectomy patients.

Computer-assisted spectral electroretinography (CASE), using full field stimulation in the presence of a rod saturating background light, has been found to be a useful means of evaluating retinal function in patients with vitreal opacities. By this means, cone electroretinograms (ERGs) to white as well as spectrally selective stimuli could easily be detected in 22 of 24 eyes with vitreal opacities obscuring any view of the fundus and with minimal or no detectable ERGs to standard single flash stimuli. The responses to spectral stimuli in the presence of a rod saturating background light provides a means of estimating the optical density of the opacity. The results indicate that most patients undergoing vitrectomy for such opacities have considerable superimposed retinal damage and that the opacities themselves are seldom sufficiently dense to decrease the ERG to any great extent. Five eyes studied before and after vitrectomy indicate that successful vitrectomy has no effect on the ERG. The results suggest that CASE may be a useful substitute to the bright flash ERG for evaluating global retinal function behind an opaque media.

Adolescent

Transplantation of cultured human retinal epithelium to Bruch's membrane of the owl monkey's eye.

Human retinal epithelial cells dividing in culture have been radiolabelled with tritiated thymidine and subsequently transplanted and identified on Bruch's membrane of owl monkey by autoradiography. Such cells have been followed from 2 hours to 7 days after transplantation. The transplant cells reattach within 2 hours to the basement membrane left on Bruch's membrane after the host epithelial cells have been removed by suction after trypsinization. Within 6 to 24 hours they form a layer on Bruch's membrane with junctional complexes between cells and an apical-basal polarity characteristic of such cells in culture or after retinal detachment. After 2 to 7 days multilayers form by continued mitosis but no transplant cells invade the choroid as long as Bruch membrane is intact. Within this time macrophages begin to appear in the choriocapillaris under the transplant. These cells migrate through Bruch's membrane and between the transplant cells but have not been seen phagocytizing transplant cells. Reattachment of the neural retina to the transplant layer has not been attempted but seems technically possible.

Animals