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Biomedical subjects

M Buse

Publications and source records attributed to M Buse.

At least 19 recordsLinked to original sources
PubMed1999

Congenital thyroid disease revisited: migrational anomalies and dyshormonogenesis.

Nuclear medicine scintigraphy, in conjunction with other diagnostic tools, plays a vital role in assessing patients with congenital migrational anomalies. We present 5 patients, 4 of whom were hypothyroid and 1 patient who was euthyroid. Scintigraphic and ultrasonographic images were examined and correlated with laboratory results. These patients demonstrate the spectrum of migrational anomalies of the thyroid. Nuclear medicine scintigraphy was a valuable aid in establishing the location of the ectopic thyroid as well as its function.

Adolescent↗
PubMed1989

Lumped versus distributed thermoregulatory control: results from a three-dimensional dynamic model.

In this study we use a three-dimensional model of the human thermal system, the spatial grid of which is 0.5 ... 1.0 cm. The model is based on well-known physical heat-transfer equations, and all parameters of the passive system have definite physical values. According to the number of substantially different areas and organs, 54 spatially different values are attributed to each physical parameter. Compatibility of simulation and experiment was achieved solely on the basis of physical considerations and physiological basic data. The equations were solved using a modification of the alternating direction implicit method. On the basis of this complex description of the passive system close to reality, various lumped and distributed parameter control equations were tested for control of metabolic heat production, blood flow and sweat production. The simplest control equations delivering results on closed-loop control compatible with experimental evidence were determined. It was concluded that it is essential to take into account the spatial distribution of heat production, blood flow and sweat production, and that at least for control of shivering, distributed controller gains different from the pattern of distribution of muscle tissue are required. For sweat production this is not so obvious, so that for simulation of sweating control after homogeneous heat load a lumped parameter control may be justified. Based on these conclusions three-dimensional temperature profiles for cold and heat load and the dynamics for changes of the environmental conditions were computed. In view of the exact simulation of the passive system and the compatibility with experimentally attainable variables there is good evidence that those values extrapolated by the simulation are adequately determined. The model may be used both for further analysis of the real thermoregulatory mechanisms and for special applications in environmental and clinical health care.

Body Temperature Regulation↗
PubMed1989

Closed loop control of human body temperature: results from a one-dimensional model.

A one-dimensional model of human thermo-regulation is used to solve a variety of basic problems in determining an adequate structure of the controller for metabolic heat production, skin blood flow and sweat production. Assuming one integrated central and one integrated peripheral afferent signal the controller parameters are evaluated by analysis of the control performance. Based on a validation by experimental results this allows the determination of a first optimized set of values for controller gains and weight of skin temperature feedback. Furthermore we analyse the effect of inhomogeneous distribution of heat production and blood flow, the influence of body fat content, of controller gains, of weight of skin temperature feedback and of depth of peripheral receptors on the dynamic performance. Increase of peripheral blood flow in particular evokes essentially both an increase of energy requirement in the cold and a quicker system response. Differing rates of increase of metabolic heat production are the consequence of differing body fat content. The weight of skin temperature feedback can be limited to 5...20%, because values outside this range evoke dynamic responses incompatible with the experiments. The actual value can only be determined if there is a correct assumption for the depth of the skin receptors. The use of measured superficial skin temperatures brings about an underestimation of the peripheral afferent signal. Of the controller gains it is primarily the gain of the metabolic controller which affects the dynamic response of the system. The experimental fact of a delayed onset of sweat production after a transition from cold to heat is the consequence of a high gain of the vasomotor system.

Adipose Tissue↗
PubMed1988

Temperature profiles with respect to inhomogeneity and geometry of the human body.

Temperature profiles within the human body are highly dependent on the geometry and inhomogeneity of the body. Physical parameters such as density and heat conductivity of the various tissues and variables such as blood flow and metabolic heat production of different organs are spatially distributed and thereby influence the temperature profiles within the human body. Actual physiological knowledge allows one to take into account up to 54 different spatially distributed values for each parameter. An adequate representation of the anatomy of the body requires a spatial three-dimensional grid of at least 0.5-1.0 cm. This is achieved by photogrammetric treatment of three-dimensional anatomic models of the human body. As a first essential result, the simulation system has produced a realistic picture of the topography of temperatures under neutral conditions. Compatibility of reality and simulation was achieved solely on the basis of physical considerations and physiological data base. Therefore the simulation is suited to the extrapolation of temperature profiles that cannot be obtained experimentally.

Body Constitution↗
PubMed1986

Staphylococcal infections in aging mice.

Aging (17 to 22 months old) and young (1 1/2 to 2 months old) mice were infected with 5 X 10(7) staphylococci. Twenty-eight-day mortality was 70% in senescent mice and 14.3% in young mice. Phagocytosis and intracellular killing of staphylococci by polymorphonuclear leukocytes and mononuclear cells and leukocyte mobilization were studied after intraperitoneal infection. Intracellular killing by polymorphonuclear leukocytes was slightly more effective in young mice but older mice mobilized about twice as many polymorphonuclear leukocytes in a 4-hour period. In older mice the lethality of intraperitoneally-administered staphylococcal toxins and salmonella endotoxin was markedly increased, the mortality rates in old and young mice being virtually identical to those found after intravenous infection with living staphylococci.

Aging↗
PubMed1986

Mespirenone and other 15,16-methylene-17-spirolactones, a new type of steroidal aldosterone antagonists.

The ability of a series of 15,16-methylene-spirolactones in comparison to known antimineralocorticoids to inhibit the renal actions of aldosterone was tested in adrenalectomized, glucocorticoid-treated rats. The standard procedure involved continuous i.v. infusion with an isotonic solution of low sodium content (0.05% NaCl + 5.2% glucose, 3 ml/rat/h) supplemented with d-aldosterone [1 micrograms/(kg X h)] resulting in a long-lasting reduction of renal sodium excretion, increase of renal potassium excretion and hence decrease of the urinary Na/K-ratio. In some experiments sodium input was increased (0.2% NaCl + 4.3% glucose or 0.9% NaCl, respectively). The test drugs either were administered orally 1 h before start of the infusion or were added to the infused solution. With the exception of two steroids which could only be tested at single doses, all compounds were administered at three doses ranging from 2.2 to 40 mg/kg (p.o.) or from 0.83 to 6.7 mg/kg/h (i.v.). Spironolactone or spirorenone (oral administration) and potassium canrenoate (i.v. infusion) served as reference compounds. The antimineralocorticoid activity of the steroids was judged by the increase in the aldosterone-lowered Na/K-ratio in urine which was collected at hourly intervals for 15 or 21 h, respectively. Adrenalectomized, glucocorticoid-treated rats receiving an i.v. infusion without aldosterone were used as controls. To obtain preliminary information on potential antiandrogenic and progestogenic (side-)effects, binding of the test-compounds to androgen receptors (rat prostate cytosol) and progestogen receptors (rabbit uterus cytosol) was measured in vitro using 3H-dihydrotestosterone (DHT) and 3H-progesterone (prog.) as tracer and unlabelled DHT and prog. as references. All steroids tested exhibited antimineralocorticoid activity. For compounds tested at three doses levels the potency relative to the standard used was evaluated using regression analysis based on the Na/K-ratio or the log (Na X 100)/K-ratio. The relative potency of the other compounds was estimated by comparing the biological effect of single doses of test drug and standard drug, respectively, using nonparametric statistical tests.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Heat balance of the human body: influence of variations of locally distributed parameters.

Human body temperature control is characterized by a local dependence of system variables and parameters. Essential properties regarding inhomogeneity of the passive system have been investigated using mathematical methods. The general diffusion-equation has been solved using implicit finite difference methods with nonlinear boundary conditions. In order to allow comparison with experimental results, a simple ideal controller has been defined. On the basis of an inhomogeneous cylinder model with four concentric layers, influences of variations due to differences between tissues and individuals or measurements of parameters such as basal metabolism and conductivity have been studied. Stationary temperature profiles calculated for homogeneous and inhomogeneous conditions have been compared. Finally, the influence of blood flow has been discussed, as well as the stationary behaviour of profiles due to blood flow and blood flow control. The change of sign of curvature of temperature profile is possible only if blood flow mechanisms and the local distribution of metabolism are taken into account.

Air↗
PubMed1985

Progestogens with antimineralocorticoid activity.

The ability of 11 steroids with varying degrees of progestogenic potency to inhibit the renal actions of aldosterone was tested in adrenalectomized, glucocorticoid-treated rats. The rats were continuously infused with an isotonic solution of low sodium content (0.05% NaCl + 5.2% glucose, 3 ml/rat/h) supplemented with d-aldosterone [1 microgram/(kg X h)] resulting in a long-lasting reduction in renal sodium excretion, increase in renal potassium excretion and hence decrease in the urinary Na/K-ratio. The test drugs were administered either subcutaneously or orally 1 h before start of infusion. Their antimineralocorticoid activity was judged by the increase in the aldosterone-lowered Na/K-ratio in urine which was collected at hourly intervals for 15 or 21 h, respectively. Adrenalectomized, glucocorticoid-treated rats receiving an i.v. infusion without aldosterone were used for assessing possible mineralocorticoid effects of the steroids tested. D-Norgestrel, norethisterone acetate, 3-keto-desogestrel (the active metabolite of desogestrel) and cyproterone acetate, respectively, did neither show antimineralocorticoid nor mineralocorticoid activity when injected subcutaneously at a dose of 53.3 mg/kg. In contrast, gestodene (26.7 or 53.3 mg/kg s.c., respectively), progesterone (53.3 mg/kg s.c.), spironolactone (26.7 mg/kg s.c.), spirorenone (13.3 mg/kg s.c.), 1,2-dihydro-spirorenone (13.3 mg/kg s.c.), or 1,2 alpha-methylene-spirorenone (13.3 mg/kg s.c.) exhibited significant anti-mineralocorticoid activity. Canrenone (53.3 mg/kg s.c.) slightly increased the urinary Na/K-ratio. This effect, however, was not significant. Gestodene, like spironolactone or progesterone, was devoid of aldosterone-like mineralocorticoid activity. With the exception of progesterone, the antimineralocorticoid activity of the steroids tested could also be demonstrated after oral administration. Based on the Na/K-ratio or the log (Na X 100)/K-ratio, the potency of each test compound relative to spironolactone was evaluated using regression analysis. The following results (average relative potency, spironolactone = 1.0) were obtained: gestodene: approximately 0.2; canrenone: approximately 0.3-0.35; spirorenone: approximately 7-8; 1,2-dihydro-spirorenone: approximately 8; 1,2 alpha-methylene-spirorenone: approximately 3.5. Progesterone which was evaluated after s.c. injection exhibited an average relative potency of approximately 0.35. Due to these results, gestodene may be regarded as the first progestogen of the nortestosterone series exhibiting a more natural, progesterone-like profile of activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1984

Properties of central control of body temperature in the rabbit.

The structure of the central temperature controller in rabbits has been analysed. On the one hand, experiments were carried out to obtain the necessary data for system analysis; on the other hand, a mathematical model of the passive system was developed which describes the thermal characteristics of the body in accordance with the experimental results. In applying the model, different controller equations for the effector mechanisms involved were tested to fit the experimental data best. They are compared with already existing models of metabolic control. In addition, mechanisms of the effector coordination are discussed. It is shown that the three effectors make use of a similar controller structure that feeds core temperature as well as skin temperature back into the controller. The system is insensitive to variations of the controller gains, whereas a slight change in the controller reference temperature causes significant changes of the controlled core temperature. Furthermore it is shown that any mutual effector blockings are dispensible.

Animals↗
PubMed1984

The renal action of spirorenone and other 6 beta,7 beta; 15 beta,16 beta-dimethylene-17-spirolactones, a new type of steroidal aldosterone antagonists.

The aldosterone antagonistic activity in vivo and the affinity for mineralocorticoid receptors (MCR) in vitro of 3-(17 beta-hydroxy-6 beta,7 beta; 15 beta,16 beta-dimethylene-3-oxo-1, 4-androstadiene-17 alpha-yl) propionic acid gamma-lactone (spirorenone), a new aldosterone antagonist, and four of its derivatives were studied in comparison with spironolactone in rats. Spirorenone was 8.6 times as potent as spironolactone, but showed a lower affinity for the MCR than the standard. The C1/C2 saturated derivative (compound I) had 7.6 times the antialdosterone potency and 2 times the binding activity of spironolactone. The 17-spiroether derivative of spirorenone (compound II) showed a lower aldosterone antagonistic activity (1.7 the potency of spironolactone) as well as a lower affinity for the MCR (0.5 the affinity of spironolactone). The analogue with a 17 beta-hydroxyl group and a 17 alpha-hydroxypropyl side chain (compound III) possessed a very low binding capacity for MCR (1/10 of that of spironolactone) but still a 1.3 times higher antialdosterone activity than spironolactone. This result is probably due to a transformation of compound III to an active metabolite in vivo. Finally, the derivative with a reversed configuration of the 17-spirolactone ring (compound IV) had no biological activity in vivo and no affinity for the MCR. These results show that spirorenone or one of its active derivatives might lead to a new series of potent aldosterone antagonists.

Adrenalectomy↗
PubMed1983

Comparison of the vasodepressor action of ZK 36 374, a stable prostacyclin derivative, PGI2 and PGE1 with their effect on platelet aggregation and bleeding time in rats.

ZK 36 374, a new, chemically stable prostacyclin derivative, was compared with PGE1 and PGI2 with respect to its action on platelet aggregation in vitro, on bleeding time and on arterial blood pressure in conscious rats. The time of occlusion of a hole in a polyethylene (PE) tube of an AV-shunt between the left carotid artery and the right jugular vein by a microthrombus was considered as an index of bleeding time. All three substances inhibited the ADP-induced aggregation of human and rat platelets. In human PRP, ZK 36 374 was 17 times more active than PGE1 and 2 - 5 times as potent as PGI2. In contrast, in rat PRP, PGI2 was 9.2 and 3.4 times as potent as PGE1 and ZK 36 374, respectively. Similar differences in potency were found in the in vivo experiments where these substances given by an intravenous infusion to conscious rats prolonged bleeding time and depressed mean arterial pressure in a dose-dependent manner. ZK 36 374 was also orally active. At oral doses of 1, 2 and 3 mg/kg this new compound caused a dose-dependent prolongation of bleeding time and a fall in arterial blood pressure. In conclusion, the results show that ZK 36 374 is an intravenously and orally active prostacyclin derivative which may be of therapeutic value for occlusive peripheral vascular diseases.

Alprostadil↗
PubMed1982

Detection and comparative evaluation of aldosterone antagonists in glucocorticoid-treated, adrenalectomized rats.

An improved method for the evaluation of aldosterone antagonists in adrenalectomized, glucocorticoid-treated rats is described. The method involved assessing the pharmacological effects of spironolactone and potassium canrenoate and comparing them with the action of prorenone and potassium prorenoate, respectively. Adrenalectomized rats were pretreated with fluocortolone caproate (10 mg/kg s.c.), a long-acting glucocorticoid, immediately after surgery. Fluocortolone (1.25 mg/kg s.c.), a short acting preparation, was administered 4 days after this treatment. On the 5th day after adrenalectomy, the actual diuresis experiment was performed. The rats received a continuous i.v. infusion of aldosterone [1 microgram/(kg x h)] for 10, 15 or 20 h. Spirnolactone or prorenone (6.7, 13.4 or 26.8 mg/kg of each steroid) were administered in single oral doses 1 h before or 4 h after the start of the i.v. infusion. Potassium canrenoate and potassium prorenoate (1.9, 3.8, or 6.7 mg/(kg x h) of each compound) were infused intravenously over 10 or 15 h. Urine was collected in 1 h fractions and the anti-aldosterone activity was assessed by the ability of the compounds to reverse the aldosterone effect on the Na/K ratio. The anti-aldosterone activity of the steroids studies was clearly detectable with the method described. Prorenone was as potent as spironolactone and potassium prorenoate was on the average 3.9 times as potent as potassium canrenoate. The method appears suitable for the characterization of the time course and duration of anti-aldosterone activity and for the calculation of relative potencies in comparison to standard compounds.

Adrenalectomy↗
PubMed1982

Age-dependent differences in outcome of infections, with special reference to experiments in mice.

The host defects that increase either the frequency or the severity of certain infections in older persons are reviewed briefly. The major defect is in the functioning of the lymphocyte-macrophage system; this is expressed as deficits in cutaneous reactivity and T cell response after antigenic stimulation. A review of induced infections in experimental animals shows results generally consistent with the data in humans. Infections due to Listeria monocytogenes, Salmonella typhimurium, and Toxoplasma gondii all appear to be worse in senescent mice; each of these organisms is dealt with primarily by the lymphocyte-macrophage system. We have recently completed studies on aged mice infected with Staphylococcus aureus, an organism dealt with primarily by polymorphonuclear leukocytes rather than the lymphocyte-macrophage system. Surprisingly, staphylococcal infections were much worse in older animals. These studies suggest that in older mice there may also be a defect either in polymorphonuclear leukocyte mobilization and/or function or in the ability of older mice to resist the lethal effects of staphylococcal toxins.

Aged↗
PubMed1982

Modification of an experimental mouse Candida infection by human dialyzable leukocyte extract.

Human dialyzable leukocyte extract (10(7) - 10(8) leukocyte equivalents, containing transfer factor) was administered intraperitoneally to CFW mice the day of and 2 days after intravenous infection with Candida albicans. Tissue Candida populations were determined immediately after and 2, 4, 7 and 14 days after infection. Kidney populations were significantly reduced on 27% of the days studied. Similar reduction in C. albicans census was obtained after injection of leukocyte extracts from donors skin test-positive to Candida antigens or donors negative to Candida antigens by skin test and migration inhibition analyses. There was no evidence of a dose-response relationship for leukocyte extract in the range 10(5) - 10(9) leukocyte equivalents. When mice were primed with C. albicans antigen 4 weeks prior to challenge the efficacy of leukocyte extracts was not augmented. There was no evidence that the infection-reducing effects were related to augmented polymorphonuclear leukocyte mobilization, increased mononuclear clearance of C. albicans, or to a direct toxic effect on C. albicans blastospores. These studies suggest that the reduction in Candida populations was non-specific and give further impetus to the use of the dialyzable leukocyte extracts as non-specific supplements to antibiotics in overwhelming or recalcitrant infections in man.

Animals↗
PubMed1981

Serum levels of arabinitol in the detection of invasive candidiasis in animals and humans.

Arabinitol is a pentitol generated in large quantitites by several species of Candida, including Candida albicans. The level of arabinitol in the sera of infected animals and humans was determined by gas-liquid chromatography of an acetone extract of the serum. Experimentally infected mice with pyelonephritis due to C. albicans had elevated levels of arabinitol; rabbits with pyelonephritis did not have elevated levels, nor did rabbits with catheter-induce cystitis, but rabbits with endocarditis developed elevated levels of arabinitol shortly before death. A prospective study in patients clinically suspected of having invasive candidiasis failed to show elevated levels of arabinitol in most. Mice and patients not colonized or infected with yeasts but with renal failure had high serum levels of arabinitol. The data indicate that an elevated level of arabinitol in the serum of a patient without renal disease is suggestive of invasive candidiasis, but normal serum levels do not contradict the diagnosis.

Adult↗
PubMed1981

Composition of tobaccos from countries with high and low incidences of lung cancer. I. Selenium, polonium-210, Alternaria, tar, and nicotine.

Tobaccos from countries with high and low incidences of lung cancer were analyzed. Tobacco concentrations of polonium-210 were similar in cigarettes from high- and low-incidence countries, as were levels of cigarette smoke tar and nicotine. Tobaccos from low-incidence countries had significantly lower Alternaria spore counts. Mean selenium concentrations of tobaccos from the high-incidence countries (0.16 +/- 0.05 micrograms/g) were significantly lower than those of tobaccos from the low-incidence countries (0.49 +/- 0.22 micrograms/g).

Alternaria↗