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Biomedical subjects

F Neumann

Publications and source records attributed to F Neumann.

At least 73 records · Page 4Linked to original sources

Two level entry concept for analog digital conversion package: usage as blackbox or toolkit.

Analog/Digital conversion of up to 16 channels can be set up and executed interactively with sampling rates individually adjusted for each channel. Additionally, asynchron and parallel digital I/0 is provided, including the possibility of triggering the beginning and the end of data acquisition on an external TTL signal. For non-experienced personnel the package can be run fully interactively with help-menus. Conversely, the experienced user can skip the menu level and directly access the A/D conversion card at the programmers' level in FORTRAN, BASIC or PASCAL. This two level approach considerably enhances the versatility of the package. Data structures in memory and on disk are the same for both levels. Thus, data acquired in menu mode can be compatibly accessed and evaluated from the menu--as well as the programmers' level. Furthermore, a concept is presented for a most efficient and convenient transfer of pre-processed data onto an IBM-mainframe for further analysis in SAS. This transfer scheme allows for continued transparency of the data files, should--for technical reasons or due to changes in the type of data acquired--changes or upgradings of the A/D conversion software become necessary. The package is available for IBM-XT/AT personal computers.

Analog-Digital Conversion↗

Clinical evaluation of pressure-controlled intermittent coronary sinus occlusion: randomized trial during coronary artery surgery.

Pressure-controlled intermittent coronary sinus occlusion (PICSO) was evaluated in a randomized trial in 30 patients undergoing bypass surgery. PICSO was applied for one hour during early reperfusion. Myocardial function was determined from short-axis cross-sectional views of intraoperative two-dimensional echocardiography. Changes of sectional and segmental wall motion during extracorporeal circulation were analyzed. Although sectional wall motion did not change significantly, hypokinetic segments were preserved better in PICSO-treated patients than in controls (-1.3 +/- 2.4 versus -9.1 +/- 2.6 delta% fractional area change; p less than 0.04). Although not significant, the same trend was found for normal and severely hypokinetic segments. Cumulative enzyme release was related to coronary sinus occluded pressure (r = 0.94; p less than 0.006), indicating washout of metabolites during PICSO. Three months after operation, functional classification was similarly favorable in both groups. Long-term effects of PICSO cannot be predicted because PICSO was applied only during early reperfusion. We conclude that PICSO is a safe procedure and that its short-term beneficial effects on myocardial function suggest a preservation of myocardial viability.

Catheterization↗

Computation of derived diagnostic quantities during intermittent coronary sinus occlusion in dogs.

The haemodynamic responses to pressure controlled intermittent coronary sinus occlusion (PICSO) were recorded intraoperatively in dogs. After analogue-digital conversion the data for coronary sinus pressure were submitted to numerical analysis for detection of systolic and diastolic envelopes and their subsequent fitting by a non-linear model. From the model variables derived quantities, such as plateau and rise times, were constructed so as to resemble the most important features of coronary sinus pressure rise during each occlusion-release cycle. The derived quantities were then monitored during all consecutive cycles throughout the entire experiment. In each dog the measurements were taken during normal coronary artery perfusion, left anterior descending coronary artery infarction, and reperfusion. The analysis comprise time course, stability, and physiological correlates of the derived quantities, on some of which a closed loop regulation may be based. Predicted plateaus (systolic and diastolic) and mean integrals (systolic and diastolic) were found to be stable quantities which, on subaveraging of about five successive estimates, yielded a 10% accuracy on the mean. By contrast, the rise times required subaveraging of about 15 cycles to achieve the same relative stability. It is concluded that, on subaveraging, derived quantities lend themselves for closed loop regulation input. Thus this quantitative assessment of numerical coronary sinus pressure analysis, as obtained from animal data, may lay the basis for future human application.

Animals↗

Intermittent coronary sinus occlusion in humans: pressure dynamics and calculation of diagnostic quantities.

Pressure controlled intermittent coronary sinus occlusion (PISCO) was applied in 30 patients undergoing coronary artery bypass surgery. The occlusion and release times were manually adjusted according to visual control of the intraoperatively monitored coronary sinus pressure. In six patients the coronary sinus measurements were additionally digitised with a personal computer before postoperative mathematical analysis, which comprised automatic detection of systolic peaks, diastolic troughs, and the calculation of derived quantities. The purpose of the analysis was (a) to assess quantitatively human coronary sinus pressure dynamics, (b) to determine whether visual control and interpretation of coronary sinus pressure rise could be replaced by a mathematical model, and (c) to ascertain whether the occlusion and release cycle lengths were adequate. Numerical estimates for intraindividual and interindividual spread of calculated quantities were produced, the mathematically obtained results were related to a possible physiological interpretation, and the most efficient method of statistical analysis was ascertained. These results form the numerical basis for a closed loop adjustment of pressure controlled intermittent coronary sinus occlusion cycling.

Aged↗

[Contraception with steroids in the male. Experimental basis].

UNLABELLED: Inhibition of spermatogenesis is possible with many types of steroid hormones. Theoretically they could be used alone or in combination for male fertility control. PROBLEMS: Oral active androgens or anabolic steroids when given in doses needed to inhibit spermatogenesis are liver toxic. Injections or administration of depot preparations every 14 days or 4 weeks is not practicable. Azoospermia or oligozoospermia does not occur immediately and examination of the ejaculate would be necessary to be sure whether and when azoospermia is achieved. Patients with oligozoospermia are not always infertile. It is known from animal experiments and from prostatic carcinoma patients that after long term suppression of pituitary function by treatment with steroid hormones the hypothalamic pituitary system becomes adapted to the high hormone levels and starts to secret gonadotrophins again. Consequently spermatogenesis is no longer fully inhibited. Regular controls of the ejaculate would be necessary to be sure, that azoospermia still persists. Spermatogenesis is also inhibited by synthetic progestogens. As compared with the doses in oral contraceptives, the doses needed for inhibition of spermatogenesis are at least 10x higher. When given alone there is also a loss of libido and potency which demands additional substitution with androgens. Concerning antiandrogens it will not be possible to find a dose for men which is reliably antifertile but which does not affect other androgen-dependent functions including libido. GnRH-agonists and antagonists have to be combined with an androgen. But there are some other still unsolved problems. IN CONCLUSION: A method for fertility control in men based on steroid hormones will not be realized in the next future.

Contraceptive Agents, Male↗

Induction of estrogen-related hyperplastic changes in the prostate of the cynomolgus monkey (Macaca fascicularis) by androstenedione and its antagonization by the aromatase inhibitor 1-methyl-androsta-1,4-diene-3,17-dione.

The cynomolgus monkey was selected as an experimental model to investigate the role of estrogens in the pathogenesis of benign prostatic hyperplasia (BPH) because its prostate seems to be more like the human prostate than that of other primate species. The treatment of intact, adult animals with the aromatizable substrate androstenedione for 3 months resulted in no significant changes in prostate weight, but in microscopically clearly detectable estrogen-related hyperplastic changes, particularly in a marked smooth muscle activation. These effects were antagonized by simultaneous, subcutaneous treatment with the aromatase inhibitor 1-methyl-androsta-1,4-diene-3,17-dione (1-Methyl-ADD) and only partially reversed by oral treatment. The serum estradiol (E2) concentration, which was not significantly elevated after treatment with androstenedione in comparison to the control, was drastically decreased after subcutaneous treatment with 1-Methyl-ADD and moderately decreased after oral treatment. In conclusion, these results as well as the great anatomical and histological similarities between the prostate of the cynomolgus monkey and that of man indicate that it might be a suitable and interesting model for future BPH studies.

Androstenedione↗

Model of the haemodynamic reactions to intermittent coronary sinus occlusion.

Coronary sinus pressure data have been obtained from anaesthetized dogs during pressure controlled intermittent coronary sinus occlusion. It is the main aim of this paper to provide a mathematical procedure for modelling the typical time course of sinus pressure after temporary obstruction of the sinus. The model is produced by fitting a parameterized function to the systolic and diastolic pressures in order to represent mathematically the shape of the curves. The parameters characterize the rise in coronary sinus pressure following occlusion, and are used to calculate 'derived quantities' which mimic the physician's visual assessment of trace recordings and their clinical implications in certain forms of coronary sinus pressure reaction. This procedure should be thought of as a kind of pattern recognition which reflects the changing state of the myocardium. The mathematical results are shown to bear a close resemblance to the clinical effects of coronary sinus occlusion.

Animals↗

[Hormonal principles in normal and pathologic somatic sexual development].

Normal sexual development is the consequence of three sequential interrelated processes: establishment of genetic, gonadal and somatic sex. It is the terminal phase of sexual differentiation--the translation of gonadal into somatic sex, which is governed by the presence or absence of both testosterone and Müllerian-inhibiting hormone and of dihydrotestosterone, which is formed in its respective target tissues. Thus, despite a testis, somatic male sexual differentiation will proceed to a normal male phenotype only if all three hormones are synthesized and act during a critical period of uterine development. Many clinically distinct syndromes are the results of abnormalities in the synthesis or action of the above-mentioned hormones; these syndromes are described in detail. In contrast to male somatic differentiation, female somatic development is independent of these hormones.

Adolescent↗

Development of a model for the induction of estrogen-related prostatic hyperplasia in the dog and its response to the aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione: preliminary results.

Although the presence of the testes is an absolutely necessary prerequisite for benign prostatic hyperplasia (BPH) to occur, the role of androgens in the cause of BPH is still controversial. There are increasing signs for a decisive role of estrogens in that connection. We treated castrated beagle dogs of known age with androstenedione (an androgen that can be aromatized) and with the aromatase inhibitor 4-hydroxyandrostendione. Six or 9 months of treatment with androstenedione resulted in a BPH characterized by typical androgenic effects--ie, hyperplasia and hypertrophy of the epithelium--and by typical estrogenic effects--, stimulation of the stroma, especially of the smooth muscles, and cystic enlargement of the tubules. These estrogen-related effects could be clearly antagonized by the simultaneous treatment with the aromatase inhibitor 4-hydroxyandrostenedione. The hyperplastic effects on the epithelium were also partly antagonized by the aromatase inhibitor. Our preliminary results further strengthen the effectiveness of aromatase inhibitors as an alternative treatment of human BPH, which is thought to be predominantly a stromal disease.

Androstenedione↗

Pharmacology of antiandrogens.

Principally, antiandrogens affect all androgen-dependent organs and functions as for instance accessory sexual glands, spermatogenesis, skin and skin appendages, libido and potency, male sexual differentiation, longitudinal bone growth and bone maturation. Pharmacologically, it is important to distinguish between the steroidal antiandrogens of the cyproterone acetate type and the nonsteroidal pure antiandrogens (flutamide, anandrone). For the clinical use of cyproterone acetate and similar antiandrogens in both men and women the three main properties are important: Cyproterone acetate is antiandrogenic, it is a quite potent progestogen and it is antigonadotrophic. Based on pharmacological and biochemical backgrounds cyproterone acetate is used in the following indications: Androgen mediated disorders of the skin such as acne, seborrhoea, hirsutism, alopecia, advanced prostatic carcinoma, precocious puberty and male hypersexuality. In order to avoid undesired systemic side effects local application of antiandrogens, e.g. of cyproterone acetate, has been tried several times. All these attempts have failed probably because insufficient concentration of the antiandrogen at the pilo sebaceous unit. 17 alpha-propylmesterolone is active when given topically (hamster ear model) and has no systemic antiandrogenic effects. This antiandrogen is highly lipophilic and does penetrate preferentially through the hair follicle as has been shown by autoradiography.

Acne Vulgaris↗

[Regulation and determinants of sex behavior].

One has to distinguish masculine sex behavior and estrogens alone or in combination with gestagens evoke feminine sex behavior. The central integrator for the induction of sex behavior is located in diencephalic nuclei. If sex hormones are lacking, the sex drive is fading off, except in women. Sex hormones are also responsible for the determination of those neutral centres controlling male or female sex behavior later in life in most species. Based on animal datas and on retrospective inquiries of homosexuals or mothers of homosexuals, a hypothesis for the etiology of homo-, bi- and hyposexuality has been developed by Dorner. Absence or deficiency of androgens in the critical phase of "brain differentiation" leads to male homo-, bi- or hyposexuality, respectively. If androgens become active in the critical phase of female differentiation, then the result will be female homo-, bi- or hyposexuality, respectively. This hypothesis will be critical evaluated.

Adolescent↗

Effects of drugs and chemicals on spermatogenesis.

Many drugs and chemicals have been found which interfere with the process of spermatogenesis. Among these substances are, for example, sex-hormones (androgens, antiandrogens, estrogens, progestogens, anabolics), chemotherapeutics, antibiotics, antifungal drugs, anticancer drugs, nonsteroidal antiinflammatory drugs, antihypertensives, neuroleptics, dopaminantagonists, indols, tranquilizers, tricyclic antidepressives, heavy metals (Co, Cd), MAO-inhibitors, antimetabolites, barbiturates, immunosuppressives (glucocorticoids), aldosteronantagonists, anticonvulsives, and perhaps alcohol and nicotine. Concerning the mechanism by which spermatogenesis is effected several points of interference have to be considered: inhibition of gonadotrophin secretion, inhibition of enzymes involved in androgen biosynthesis, direct effects on the germinal epithelium or on Sertoli cell function, competitive inhibition of hormone action, damage of the blood-testes barrier and other mechanisms. Some of these mechanisms will be discussed.

Animals↗

Anti-oestrogenic effects of tamoxifen on mammary gland and hypophysis in female rats.

Adult ovariectomized rats were treated for 14 days with oestradiol benzoate (E2B) 15 micrograms/kg/d and oestradiol benzoate 15 micrograms/kg/d + progesterone (PRO) 15 mg/kg/d for induction of mammary gland parenchymal stimulation. Histological examination and whole mount preparation demonstrated that ductal growth in the mammary gland after E2B treatment was completely antagonized by tamoxifen (TAM) 0.5 mg/kg/d. Parallel DNA concentrations in the mammary gland were decreased to control levels by TAM 0.5, 5 and 15 mg/kg/d. E2B-induced hyperprolactinaemia in the forenoon (basal secretion was equally reduced by TAM 0.5, 5 and 15 mg/kg/d). In the afternoon, when prolactin (Prl) secretion is at its maximum, TAM 0.5 mg/kg/d turned out to be ineffective to abolish Prl surge, but TAM 5 and 15 mg/kg/d reduced serum Prl concentrations in a dose-related manner. Immunoperoxidase staining of Prl cells in the pars distalis of the hypophysis indicated that adaptive hypertrophy and signs of hypersecretion after E2B were abolished by TAM 5 mg/kg/d. Luteotrophic cells clearly showed cellular atrophy, regression and secretory inactivity. Maximal tubulo-alveolar mammary parenchymal stimulation in rats treated with E2B-PRO was slightly inhibited by TAM 0.5 mg/kg/d. Histology showed a small disseminated parenchymal islet. DNA concentrations only were partially decreased by the anti-oestrogen though serum Prl concentrations were found to be completely decreased to control levels. Secretory activity of Prl cells was reduced by TAM 0.5 mg/kg/d. In E2B-PRO treated rats lisuride had poor inhibitory activity on Prl levels and none on DNA concentrations in the mammary gland. Combined treatment with TAM and lisuride significantly decreased DNA concentration in the mammary gland compared to animals which received E2B-PRO. Also Prl levels were at a minimum. Histology performed on the mammary gland showed only slight tubulo- but no tubulo-alveolar activation. Luteotrophic cells in the pituitary gland stained by the immunoperoxidase technique appeared regressive, shrunken and atrophied.

Animals↗