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F Neumann

Publications and source records attributed to F Neumann.

At least 37 records · Page 2Linked to original sources
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

[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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1979

Evaluation of effects of sexual steroids on the hypothalamic-pituitary system of animals and man.

Specific neuroendocrine regulatory mechanisms in rats and mice are known to be involved in the development of pituitary tumours (prolactinomas) in systemic tolerance and carcinogenicity studies of oestrogens, certain progestagens and their combinations. However, the susceptibility of the strain used seems to be of decisive importance. High doses of oestrogens may also, in special cases, stimulate development of PRL cell hyperplasia and tumours in humans. In other species such as the hamster long-term treatment with oestrogens results in hyperplastic and neoplastic changes in MSH-producing cells of the pars intermedia of the pituitary gland. On the other hand, in the dog and monkey, steroid-related pituitary tumours were not observed, in spite of long-term treatment with high doses of oestrogens, progestagens and their combinations. The capability of certain progestagens to stimulate canine GH secretion seems to play a major role as mediator of the species-specific progestagen-induced changes (mammary tumours, diabetes- and acromegalic-like syndrome) in the beagle dog. These progestagens also seem to have, in addition to their antigonadotrophic properties, an inhibitory effect on CRH-ACTH and TRH-TSH activity in the beagle bitch. These effects can be demonstrated in both the hypothalamic-pituitary system and in the corresponding peripheral target organs. These findings in the dog were not comparable to the situation in other species including man. The extent to which all these results in different species are applicable to other species depends on whether their neuroendocrine control systems are qualitatively and/or quantitatively similar. The physiological significance of the different pituitary hormones, sensitivity of target organs as well as a certain genetic disposition in the different species should also be considered. All these factors can vary from species to species. From these facts, it can be easily appreciated that results of experiments on different species with a substance possessing the same quality of biological effect in these species (e.g., oestrogen, progestagen, etc.) can only be compared when the experimental procedure takes account of the effect of this substance on the neuroendocrine system of the different species, and when dosage, mode of administration and period of treatment are correspondingly matched to the physiological conditions of each species.

Animals↗
PubMed1979

Estrogenic partial effect of norethisterone enanthate in relation to tumor induction in rat mammary gland.

The tumorigenic effect of norethisterone enanthate (NE) on mammary glands in rat and mouse may be ascribed to its own inherent estrogenicity, which is especially pronounced in these species. Because of the estrogenic partial effect, NE stimulates tubulo-alveolar growth of rat mammary gland intensively as does an estrogen-progesterone combination. Although prolactin is known as one of the essential factors needed for development of rat mammary gland, NE causes only a slight increase in serum prolactin level in the rat. In contrast with rat and mouse, NE exerts only a progestational effect in the rabbit. Since the estrogenicity of NE has not been found in many clinical studies, the estrogenic partial effect of NE seems to have no significance in humans. Such a species difference is finally due to the fact that the optimal dose ratio between estrogens and progesterone for maintenance of physiological functions of target organs is quite different from species to species.

Animals↗
PubMed1979

Role of the pituitary gland in experimental hormonal induction and prevention of benign prostatic hyperplasia in the dog.

The antiandrogen, cyproterone acetate (CPA), prevents development of prostatic hyperplasia, induced in castrated dogs by a 6 month-treatment with 5 alpha-androstane-3 alpha, 17 beta-diol (A)alone or in combination with 17 beta-oestradiol (E2). The immunoperoxidase technique was used to study functional cell types in the pars distalis of the pituitary gland and to detect growth hormone (GH) and prolactin (PRL) target sites in the prostate gland. Homologous radioimmunoassays for estimation of serum canine GH and PRL concentrations were also performed. Treatment with the combinations A + E2 and A + E2 + CPA resulted in morphological indications of stimulated GH and PRL cells and depressed gonadotrophs. This correlates well with an increase in PRL-dependent staining in glandular epithelium and fibromuscular tissue of the prostate gland. However, basal serum PRL and GH levels were not significantly affected. Treatment with A and A + E2 stimulated, while additional treatment with CPA clearly suppressed adrenocorticotrophin/melanotrophin (ACTH/MSH) cells. These findings indicate that an endocrine imbalance in hypothalamic-pituitary-adrenal function may be involved in induction and prevention of prostatic hyperplasia in the dog.

Androstane-3,17-diol↗
PubMed1979

Biochemical and histological studies on prostates in castrated dogs after treatment with androstanediol, oestradiol and cyproterone acetate.

The effect of cyproterone acetate (CA) on experimentally induced benign prostatic hyperplasia (BPH) in the castrated dog was investigated. BPH was induced by 6 months' treatment with 3 alpha-androstanediol (3 alpha-diol) alone and in combination with 17 beta-oestradiol (Oe2). RNA, DNA and zinc content of the glands were determined in addition to histological examination and measurement of the prostates. Two different types of prostatic enlargement were observed. First, 3 alpha-diol induced typical diffuse canine hyperplasia with replacement of functional activity. DNA, RNA and the zinc content of total glands were increased compared with intact controls. Second, 3 alpha-diol plus Oe2 produced on the one hand a more striking increase of prostatic weights, but on the other a loss of typical morphological structure and function. Histologically, transformation of simple glandular epithelium into stratified squamous metaplasia occurred in addition to stimulation of fibromuscular tissue. Biochemically, a relative decrease of DNA per mg tissue was measured with a fall in the RNA to DNA ratio and zinc to the values of castrates. Administration of CA resulted in an abolition of the 3 alpha-diol effect. Biochemical determinations and histological examinations revealed an effect similar to castration after treatment with 3 alpha-diol plus CA. After treatment with 3 alpha-diol plus Oe2 plus CA fibromuscular stimulation as an oestrogen effect predominated in addition to glandular atrophy and metaplastic changes, especially in prostatic ducts. Epithelial hyperplasia is an effect of 3 alpha-diol, whereas metaplastic proliferation only occurs in oestrogenized and androgenized dogs. In both types of prostatic enlargement CA prevents development of hyperplastic prostate.

Androstane-3,17-diol↗
PubMed1978

A study of the capacity for regeneration of rat and human Leydig cells.

The capacity of Leydig cells for regeneration was investigated in 12 patients with prostatic carcinoma, who underwent subcapsular orchidectomy, and in rats after testicular necrosis produced by cadmium chloride. In rats, reappearance of Leydig cells originating from the tunica albuginea could be demonstrated by histology. Testosterone concentrations increased parallel to regeneration of Leydig cells, while LH concentrations declined. In contrast to these findings, no rise of testosterone concentrations could be observed in patients up to 8 months after subcapsular orchidectomy. Human Leydig cells seem to have no capacity for regeneration, or endocrine function, despite the fact that some of these cells, which are present morphologically in the tunica albuginea or spermatic cord, remained.

Animals↗