PubMed HealthSearch

Biomedical subjects

F Neumann

Publications and source records attributed to F Neumann.

At least 19 recordsLinked to original sources

[Transesophageal echocardiography from the surgical viewpoint].

Following the development of new techniques in echocardiography and especially of Doppler color flow imaging, a new dimension of cardiac surgery has been brought about. The use of transesophageal probes facilitates routine surgery to be performed without interferences and, also, comparability between repeated ultrasonic measurements. Originally, echocardiography was mainly applied for quality control by comparing pre- and postoperative echocardiograms. Now it is equally important in perioperative strategy planning guiding the surgeon's decision throughout the operation as well as in cardiac emergencies. Using intraoperative echocardiography routinely in cardiac surgery establishes a more and more close cooperation between surgeons, cardiologists, and anesthesiologists. In order to evaluate the clinical relevance of echo findings, they have to be repeatedly correlated to surgical realities and to long term results of clinical outcome.

Adult

Effects of coronary artery bypass grafting on global and regional myocardial function. An intraoperative echocardiographic assessment.

The immediate effect of coronary artery bypass grafting on global and regional myocardial function was studied by means of epicardial two-dimensional echocardiography during operations in 20 patients. Echocardiograms were recorded before cardiopulmonary bypass and 5 and 30 minutes after bypass. Global left ventricular function was expressed as percent short-axis area change and regional function as percent fractional area change. Segments were classified according to their baseline function as normal (percent fractional area change greater than 40%), moderately hypokinetic (percent fractional area change 21% to 40%), or severely dysfunctional (percent fractional area change less than 20%). Percent short-axis area change was significantly reduced immediately after cardiopulmonary bypass (from 42.0% +/- 4.6% to 34.9% +/- 3.0%, p less than 0.05) but had returned to baseline 30 minutes after bypass (42.6% +/- 4.0%). Similarly, function of normal and moderately hypokinetic segments decreased significantly immediately after cardiopulmonary bypass (normal segments: percent fractional area change 56% +/- 0.9% before bypass to 42.3% +/- 1.5% after bypass, p less than 0.0001; moderately hypokinetic segments: 31.0% +/- 0.9% to 25.1% +/- 1.4%, p less than 0.002). Both normal and moderately hypokinetic areas regained baseline function by 30 minutes after bypass (normal segments: 53.4% +/- 1.6%; moderately hypokinetic segments: 35.4% +/- 2.0%). In contrast, severely dysfunctional segments were found to be significantly improved immediately after bypass (14.7% +/- 0.9% before bypass to 27.7% +/- 2.1% after bypass, p less than 0.0001). This improvement was maintained 30 minutes after bypass (22.8% +/- 1.5%, p less than 0.001). We conclude that coronary revascularization exhibits an immediate beneficial effect on chronically underperfused myocardium having severely depressed baseline function. However, in normal and moderately hypokinetic areas, the depressant effects of global ischemia and reperfusion prevail in the immediate postbypass period, leading to a global depression of cardiac function.

Angina Pectoris

Early indicators for carcinogenesis in sex-hormone-sensitive organs.

Hormones induce tumours in various target tissues in different species of laboratory animals in long-term toxicity studies. Examples of such tumours are: mammary gland tumours in beagle dogs after long-term treatment with progestogens or progestogen/oestrogen combinations; pituitary and mammary gland tumours in rats and mice after long-term treatment with oestrogens or progestogens with an oestrogenic partial effect; interstitial cell tumours in rats after chronic overstimulation by endogenous luteinising hormone; endometrial carcinomas in rats after chronic treatment with dopamine agonists. As a rule every hormone when given in excessive doses over prolonged periods can induce a tumour in the relevant target organs. Drugs or chemicals which stimulate or inhibit the endogenous hormone production of certain endocrine organs can have the same effect. Tumour induction can be a direct or indirect effect involving specific regulatory mechanisms. In general, the induction is preceded by excessive hyperplasia of the target tissue concerned or with regard to the pituitary where excess production of the stimulating hormone occurs. Tumour induction in chronic toxicity studies can usually be predicted by determining hormone levels in short-term studies. Hormones and drugs or chemicals which induce tumours when given in doses high enough to induce hyperplasia are unlikely to do so by a genotoxic mechanism.

Animals

Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience.

Cyproterone acetate (CPA) has been discovered more than 25 years ago and it was the first antiandrogen suitable for clinical use. CPA inhibits the action of endogenous and exogenous androgens at all androgen target organs; these include the prostate, seminal vesicles, testes, and the vas deferens. However, this antiandrogen also antagonizes less sex-specific effects of androgens, for example ossification of the epiphyseal cartilage, sebaceous gland function and skin thickness. Indications for CPA: Prostate cancer, androgen induced disorders of the skin (acne, seborrhoea, hirsutism, alopecia), precocious puberty and sexual disorders in men. Concerning sexual deviations clinical trials started in 1966. CPA leads to loss of libido and the ability to achieve erection, followed by the inability to achieve orgasm, after about 14 days of treatment (100-200 mg daily orally or 300 mg weekly i.m.). These effects are reversed in the same order as the onset. About 75 to 80% of patients respond to this therapy. CPA is generally well tolerated. Tiredness, lack of drive, listlessness and depressive moods have been reported as non-specific side-effects. Slight gynecomastia occurs in about 20% of patients. There are no good alternatives in this indication. Pure antiandrogens are unsuitable, because these are unable to inhibit libido sufficiently. Tranquilizers are not very effective, high doses of estrogens are associated with severe (cardiovascular) side effects. Orchidectomy is an irreversible intervention, LHRH analogues are associated with hot flushes and the initial increase in testosterone (flare phenomenon).

Androgen Antagonists

Immediate effects of mammary artery revascularization versus saphenous vein on global and regional myocardial function: an intraoperative echocardiographic assessment.

The immediate effect of coronary artery bypass surgery on global and regional myocardial function using the internal mammary artery (IMA) versus saphenous vein (SV) was studied intraoperatively using transesophageal echocardiography (TEE). Thirty-two patients received an IMA and 10 patients only SV. Transesophageal echocardiography was recorded before thoracotomy, 5 minutes after the end of cardiopulmonary bypass (CPB) and after chest closure. Global and regional left ventricular function were expressed as a percent of the short axis area change (%SAAC) and a percent of the fractional area change (%FAC), respectively. Segments were classified according to their baseline function as normal, %FAC greater than 40%, or dysfunctional, %FAC less than 40%. Only normal segments were considered in this study. No significant change in %SAAC in either group was observed in this study. Internal mammary artery revascularized segments showed a significant decrease in %FAC from 57 +/- 1 before thoractomy to 53 +/- 2 5 minutes after CPB, whereas SV segments showed a significant improvement in %FAC from 56 +/- 1 to 61 +/- 1. Applying strict criteria derived from intraobserver and cycle-to-cycle variability, 17% of IMA segments had deteriorated by more than 36% whereas only 4% of SV segments showed such deterioration. Conversely, 17% of SV segments showed an increase in %FAC by more than 36% and only 3% of IMA segments improved similarily. The observed changes were of short duration and had largely resolved by chest closure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Simulation of coronary circulation with special regard to the venous bed and coronary sinus occlusion.

The vascular beds of the left circumflex and the left anterior descending coronary arteries are modelled by means of coupled differential equations that consider an arterial, a capillary and a venous section. In a stepwise procedure, experimental data from normal coronary perfusion and coronary sinus occlusion are used to assess the model parameters. For venous distensibility, a non-linear form of pressure-volume relationship proved vital to reproduce the characteristics of the rise in venous pressure after the onset of coronary sinus occlusion. Numerical integration was carried out for normal perfusion and for coronary sinus occlusion, yielding time courses of flows, volumes and pressures within large coronary arteries, capillaries and coronary veins. Coronary sinus occlusion reduces total mean flow by 18% and divides intramyocardial flow between the capillaries and the veins into a forward component of 3.03 mls-1 and a backward component of -1.54 mls-1. This result represents a prediction for a haemodynamic quantity which is therapeutically important but inaccessible to measurement. Varying degrees of systolic myocardial squeezing are studied to display the impact of myocardial contractility and vessel collapse on the mean values and phasic components of intra-myocardial flows.

Blood Pressure

The role of intramyocardial pressure during coronary sinus interventions: a computer model study.

A model consisting of an arterial, a capillary, and a venous compartment was developed to reproduce experimentally determined hemodynamic results of the arterial and venous sides of the coronary circulation. From the model, intramyocardial flow between capillaries and veins, which is inaccessable to measurement, was then estimated. Results are given for normal perfusion and coronary sinus occlusion conditions. For both conditions, intramyocardial pressure was varied within the model in order to study its impact on intramyocardial flow. For low and moderate intramyocardial pressures under coronary sinus occlusion, retrograde flow from veins to capillaries was seen to increase with increasing intramyocardial pressure. However, for very high values of intramyocardial pressure, which are close to left ventricular pressure, retrograde flow declined.

Computer Simulation

Influence of CAPD and residual diuresis on the serum levels of alpha-1-microglobulin in end-stage renal disease.

The chronic retention of proteins of low molecular weight (LMWP) seems to be connected with some unsolved problems of end-stage renal disease (e.g. reduced immune function, AB amyloidosis, hormonal imbalances), irrespective of the type of renal replacement therapy. Therefore, several recently discovered LMWPs such as alpha 1-microglobulin have to be evaluated concerning their contribution to the uremic syndrome. Although we observed a considerable daily loss of total protein into the CAPD dialysate, no differences were found in the removal of small proteins (MW less than 68 kilodaltons) when compared to conventional hemodialysis. Maintenance of renal function (residual diuresis greater than 100 ml/day) seems to be more potent keeping the serum concentrations of LMWP low than CAPD or hemodialysis.

Adult

[Endocrinologic factors in the development of benign prostatic hyperplasia].

The development of benign prostatic hyperplasia is determined by aging and a functioning testis. This concept of the pathogenesis is supported by studies showing that regression of the enlarged prostate can be achieved by means of drugs that interfere with either the synthesis or the action of testosterone. Since both these therapeutic principles lead to symptoms of hypogonadism their therapeutic value is limited. Recent observations, however, indicate the feasibility of developing agents that will relieve the obstruction of urinary outflow and cause shrinkage of the enlarged prostate without impairing the action of androgen in other tissues.

Androgens

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

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

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