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Biomedical subjects

W Krause

Publications and source records attributed to W Krause.

At least 109 records · Page 6Linked to original sources

[Diseases of the male breast].

Enlargement of the male mammary gland is termed gynaecomastia. Diagnosis and treatment of this andrological disorder usually fall to dermatologists, surgeons and primary care physicians. Gynaecomastia is found in men of different ages with frequency. The harmless pubertal gynaecomastia is as frequent as gynaecomastia of the elderly. Other forms are caused by an altered ratio of oestrogens to androgens, by hCG-producing tumours, and by hyperprolactinaemia. There is no correlation between cause and clinical appearance. Gynaecomastia is easy usually easily diagnosed by clinical examination; sonography and mammography may then be used for confirmation. Endocrine causes and hCG-producing tumours should be excluded by hormone analysis. Histological examination of the tissue is mandatory to exclude carcinoma of the breast. The prognosis of male breast carcinoma is not poorer than that of the female carcinoma. Pubertal gynaecomastia usually resolves spontaneously. Surgical removal is generally required in other forms, as conservative approaches are ineffective.

Adolescent↗

Biochemical characterization of x-ray contrast media.

RATIONALE AND OBJECTIVES: Eleven ionic and nonionic contrast media were compared in parallel regarding their effects on various biochemical parameters in vitro. Partition coefficient, protein binding, release of histamine, hemolysis inhibition and complement activation were determined as well as inhibition of various enzymes. Additionally, incompatibilities between contrast media and intravascular drugs that often are coadministered were determined. METHODS: Partition coefficients were determined in the system n-butanol/water by spectrophotometry. Protein binding was measured by equilibrium dialysis. Histamine release from rat peritoneal mast cells was measured by radioassay. Hemolysis inhibition and complement activation was determined in beagle dog serum using antibody-coated sheep erythrocytes. The inhibition of enzyme systems was measured photometrically. Incompatibility with coadministered drugs was registered by appearance of precipitations. RESULTS: Hydrophilicity as determined by partition coefficients was highest for iotrolan and lowest for iotetrol. Protein binding ranged from practically zero for most substances to 14% for ioxaglate. Histamine release was highest for diatrizoate (77% at 100 mg I/mL) and lowest for iodixanol (1%). Complement activation at 100 mg I/mL ranged from 0% (diatrizoate, iopamidol) to 77% (iopentol). The inhibition of the enzyme systems urokinase, streptokinase, collagenase, tissue plasminogen activator, and lysozyme was lowest for the nonionic dimers. CONCLUSIONS: All compounds influenced the parameters tested. However, the degree of interaction was different. Although there was no significant correlation between hydrophilicity (partition coefficient) or osmolality and the tested parameters, nonionic dimers seemed to be superior to nonionic monomers. The reason might lie in reduced chemotoxicity of this class of contrast media.

1-Butanol↗

Application of pharmacokinetics to computed tomography: injection rates and schemes: mono-, bi-, or multiphasic?

OBJECTIVE: The objective of the current study was to test whether optimization of dose regimens for detecting focal liver lesions by computed tomography is possible by using the available time-density data of former studies published in the literature and a computer program so that the number of further clinical tests with the exclusive objective of optimizing injection schemes could be reduced. METHODS: Computed tomography enhancement data of the aorta and/or the liver obtained after injecting a conventional ionic and a nonionic contrast agent were used to calculate pharmacokinetic parameters and to simulate the time course of enhancement for a variety of different infusion regimens modifying contrast medium strength, dose, and injection rate. The study consisted of two parts. In the first part, mean relative enhancement curves of the aorta and of liver parenchyma (0 to 300 sec) using meglumine diatrizoate (306 mg iodine per mL, 300 mg iodine per kg) were taken from the literature and their values were approximated using the computer program TOPFIT. In the second part, equivalent data for iohexol including a total of three strengths (240, 300, and 350 mg iodine per kg) and doses from 30 to 45 grams of iodine were used. "Validation" of the simulation method was obtained, first by comparing measured and calculated maximum intensities and times to reach maximum and, second, by using one injection scheme for the simulation of a second and comparing the results with actually measured data. RESULTS: The computer program TOPFIT allowed for excellent curve fitting of the measured density values. The data obtained in the first part of the study showed that after a dose of 300 mg I/kg and a rate of 2 mL/sec maximal enhancement is achieved in the aorta after 30 seconds (approximately 100 HU) and in the liver after 50 seconds (approximately 30 HU). The higher the dose and the rate of infusion were, the higher was the enhancement. The difference in density between aorta and liver was proportional to the infusion rate approaching asymptotically approximately 90 HU at 8 mL/sec for a dose of 300 mg I/kg. Bi- or triphasic infusion schemes did not improve differences in enhancement. The curve fitting obtained in the second part of the study also confirmed the results reported in the literature. A "crossover" prediction of data was possible within the range of interindividual variations of pharmacokinetic parameters and thus validated the chosen approach of computer simulation. Furthermore, data sets selected randomly out of the simulation results could be used--within the limits of interindividual variability--to predict data determined in other clinical trials. CONCLUSION: The computer program TOPFIT appears useful for the optimization of time--density profiles in computed tomography. The number of further clinical studies with the objective of optimization could therefore possibly be reduced.

Aortography↗

Ytterbium- and dysprosium-EOB-DTPA. A new prototype of liver-specific contrast agents for computed tomography.

RATIONALE AND OBJECTIVES: A series of studies was conducted to determine whether metal complexes of the EOB-DTPA type are useful as contrast agents for computed tomography (CT). METHODS: Metal complexes using EOB-DTPA as ligand were synthesized with lanthanide metal ions (lanthanum [La], cerium [Ce], praseodyme [Pr], gadolinium [Gd], dysprosium [Dy], ytterbium [Yb], and lutetium [Lu]) and with nonlanthanides (lead [Pb] and bismuth [Bi]). Complex stability was assessed by measuring binding to bone meal. The physicochemical parameters partition coefficient, osmolality, viscosity, and protein binding were determined in vitro. Tolerability was tested both in vitro (thromboplastin time, effect on erythrocytes) and in vivo (acute, neural, and cardiovascular toxicities). Biliary excretion and tissue distribution, especially liver, kidney, and bone concentrations, were measured in rats after intravenous doses of 0.5 mmol/kg. Imaging performance using CT was investigated in vitro in a phantom model and, for Gd-EOB-DTPA, in vivo by injecting doses of 0.5 mmol/kg into healthy or tumor-bearing rats and rabbits. RESULTS: The kinetic stability of M-EOB-DTPA complexes differed widely. Nonlanthanide metals, especially Pb-EOB-DTPA, provided less stable complexes than lanthanides with an optimum of stability for the metals Gd, Dy, Yb, and Lu. Tolerability was good for all compounds, best results were obtained for Gd and Yb. Concentrations in rat liver after administration of Gd-EOB-DTPA, 0.5 mmol/kg intravenous, were approximately 1 mumol/g, resulting in CT enhancement of 16 Hounsfield units (HU). Tumor tissue was not enhanced. In rabbits, at the same dose level 30 HU was found. CONCLUSIONS: Metal complexes of the EOB-DTPA type, especially those of Gd and Yb seem to be useful as iodine-free liver-specific contrast agents for CT.

Animals↗

Contribution of andrological factors to sterility.

Male fertility disorders contribute to sterility by inhibiting conception. The prevalence in general, is high, nearly 5% of men are subfertile or infertile. Infertility could be diagnosed in some cases by specific investigations, however, a positive prediction of fertility is not possible. Nearly half of the couples could be treated successfully. It should be recognized, however, that psychosocial assistance is one of the most important tasks of modern reproductive medicine for couples in whom the treatment was not successful.

Female↗

[Therapy of rheumatic disease with a hydroxyethylsalicylate gel. Results of 2 clinical studies of effectiveness and bioavailability].

Two clinical studies were carried out to investigate the efficacy and safety as well as the local and systemic availability of a hydroxyethylsalicyclate gel. A double blind, multicenter trial, involving 113 patients with nonarticular rheumatic back pain, revealed statistically significant relief of pain as compared with placebo. Local and systemic tolerance was excellent. An open study of bioavailability after local application in 16 patients showed a mean salicylate concentration of 0.93 +/- 0.5 microgram/ml in the synovial fluid and 0.40 +/- 0.23 microgram/ml in the synovial membrane, compared with 0.14 +/- 0.04 microgram/ml in the serum. Genetisinic acid was not detected, while OH-hippuric acid was detected only in the serum and synovial fluid.

Administration, Topical↗

[Do we need the concept of male climacteric?].

The female menopause is considered to be a result of a decrease in the endocrinal metabolic activity of the ovaries. Although the male lacks such a highly visible sign as the cessation of the menstrual flow, the amount of testosterone produced by the aging male does in fact decrease. Recent studies, such as the Massachusetts Male Aging Study show that, between the ages of 40 to 70 years, the mean testosterone level decreases annually by about 1%. Chronic diseases and the use of drugs have a comparable effect. Although it is generally believed that sexual impotence is a major symptom of male menopause, recent investigations have shown that sexual functionability may be preserved into the ninth and tenth decade of life. Sexuality is not merely an instinct or a psychological expression, but is deeply anchored within the personality. Even when, with increasing age, the frequency of sexual dysfunction increases, such changes do not correlate with the decrease in testosterone levels. None of these phenomena take place within an age span that marks them off from the involution processes in other organs. The expression midlife crisis commonly met with in the English literature points up the psycho-social implications. Impotence or a loss of sexuality is not a sequel of aging, but of attitude towards sexuality. The latter is preserved if it is not neglected throughout the course of a lifetime.

Adult↗

Dynamic power and coherence analysis of ultra short-term cognitive processes--a methodical study.

This EEG mapping study was designed to explore ultra short-term cognitive processes in human thinking. The EEG was recorded while the subjects performed two tasks randomly mixed in time: category concept activation and pattern comparison. A novel approach is introduced to examine these tasks by means of band powers and coherence with high time and frequency resolution. This approach is based on general adaptive principles and the adaptive fit of a bivariate linear model (ARMA model) with time varying parameters, and allows the estimation of band powers and coherences continuously in time. The application of mapping to these spectral parameter functions results in map sequences of band powers, and local band coherences. It was proved that these map sequences of the frequency band 13-20Hz reflect the dynamic behaviour of information processing in a characteristic topographical manner. Based on these dynamic topographical examinations, conceptual and imaginal representations are distinguishable.

Brain Mapping↗

Liver contrast enhancement in primates using iopromide liposomes.

RATIONALE AND OBJECTIVES: We studied the feasibility of using iodinated liposomes as computed tomography (CT) liver contrast agents in nonhuman primates. METHODS: Iopromide-containing liposomes were investigated as reticuloendothelial (RES) contrast agents for CT scanning of the liver in normal adult baboons. For intravenous (i.v.) injection, liposomes were resuspended in mannitol solution, filtered under sterile conditions, and injected i.v. at doses of 200 and 400 mg l/kg to each of five anesthetized adult baboons. RESULTS: Animals tolerated the injections without measurable electrocardiographic changes and recovered uneventfully from anesthesia. Sequential CT scans of the baboons' upper abdomen acquired up to 60 min postinjection showed persistent enhancement of the liver 10-60 min after injection. Maximum enhancement levels were 36 and 61 delta Hounsfield units (delta H) after the 200- and 400-mg/kg doses, respectively. The mean time to plateau enhancement was 20 min with the 200-mg/kg dose and 10 min with the 400-mg/kg dose. The greatest splenic enhancements were 181 and 301 delta H after the 200- and 400-mg/kg doses, respectively. CONCLUSION: Iopromide liposomes are effective as RES contrast agents in primates.

Animals↗

Pharmacokinetics of iopromide liposomes in rabbits.

PURPOSE: The dose-proportionality of pharmacokinetics of an iodinated contrast medium, iopromide, encapsulated into liposomes was investigated. METHODS: Following single intravenous administration of 150 mg iodine/kg (potential diagnostic dose) and a five-fold higher dose in rabbits the pattern of elimination was studied until 7 d and the blood concentrations were monitored up to 72 h after administration. The iodine concentration in the liver was calculated on the basis of the blood concentration and related to the concentration measured in the rabbit liver. RESULTS: The dose-normalized blood concentration-time profiles of the encapsulated iodine were not superimposable. Contrary to the low dose a steady-state concentration of 2.8 mg iodine/mL was observed in blood for 60 min after the high dose administration indicating a saturation of the liposomal liver uptake. For both doses the elimination of iodine occurred predominantly via the kidneys and was complete 7 d after administration. The dose-normalized amounts of iodine excreted with the urine were similar for both dose groups. From the blood data it was calculated that doses up to about 300 mg iodine/kg should result in a dose-proportional increase of liposomal liver uptake before saturation occurs. This was confirmed by the measured iodine liver concentrations after increasing the doses stepwise from 150 to 750 mg iodine/kg. CONCLUSIONS: In rabbits for the dose range 150 to 750 mg iodine/kg iopromide liposomes reveal dose-dependent pharmacokinetics due to a saturation in liver uptake which occurs for doses of 300 mg iodine/kg corresponding to 300 mg lipid/kg onwards.

Animals↗

Computer-assisted semen analysis systems: comparison with routine evaluation and prognostic value in male fertility and assisted reproduction.

Semen analysis was performed by employing a computer-assisted semen analysis (CASA) system (SM-CMA), in comparison with visual estimation by microscope. There was a significant relationship between the values obtained by both methods, but a large range of differences in individual values was observed. Results of semen analysis in 407 men complaining of reduced fertility were investigated for their relationship to fertility outcome. The parameters obtained by the CASA system were analysed in relation to time to conception, applying the Cox proportional hazards model of regression. In univariate regression analysis, all examined CASA parameters were shown to have a significant effect on cumulative hazard function. However, applying a multivariate step forward approach, only percentage of motile spermatozoa and log-transformed values of sperm count remained significant predictors of later fertility due to the close intercorrelations among the examined covariates. We concluded that the determination of elaborate motility characteristics as obtained by CASA systems is of limited value to optimizing the evaluation of male fertility status.

Adult↗

Changes in the microcirculation of the intact rat heart after iodinated and gadolinium-containing contrast media.

RATIONALE AND OBJECTIVES: A new model was developed to study microcirculation in the intact heart of the anesthetized rat, and the effects of roentgenography and magnetic resonance imaging contrast media were investigated. METHODS: Roentgenography contrast media (600 mg iodine/kg), gadopentetate (0.25 mmol/kg), or physiological saline were injected intraarterially into anesthetized rats (N = 10) whose chests had been opened in a pressurized container. The effects on arterial and venous vasomotion and microhemodynamics of the capillary network were determined in vivo by combined incidental light-fluoroscopic microscopy using continuous 35-mm cine film and video recordings from 5 minutes before until 20 minutes after injection. The amplitude and frequency spectra were evaluated according to the Prony method and by Fourier analysis. Additionally, the number of perfused vessel bifurcations were counted. RESULTS: Gadopentetate exhibited no effects on microcirculation, and diatrizoate exhibited the largest ones. The deformation of the vasomotion spectrum reached 28%, and bifurcations were reduced by 21%. The effects were reversible within 10 minutes of injection. Iotrolan showed minimal disturbance. The other contrast media (iopromide, iopamidol, ioxaglate) fell between these two extremes. CONCLUSION: High-osmolar ionic roentgenography contrast media resulted in a transient deregulation of vasomotion and in a disturbed microcirculation in the rat heart. Isotonic or low-osmolar nonionic roentgenography contrast media or gadopentetate did not show this effect or showed it only to a minimal extent.

Animals↗

The lack of immunogenicity of iotrolan.

RATIONALE AND OBJECTIVES: To test whether it would be possible to raise antibodies against iotrolan in rabbits and, if possible, to develop a radioimmunoassay for iotrolan. METHODS: A "half-molecular" analogue of iotrolan was synthesized, which contained a carboxylic group. This moiety was coupled via a link to bovine serum albumin. The resultant hapten was suspended in Freund's complete adjuvant and used to immunize rabbits by two subcutaneous and two intramuscular injections followed by monthly booster injections. After bleeding of the animals, the antibodies formed were tested. RESULTS: The rabbits successfully developed antibodies against the hapten. These antibodies were tested for cross-reactivity with iotrolan, the iotrolan half-molecule, and the hapten. Minimal cross-reactivity (below 0.5%) was found for iotrolan and the half-molecule. Only the hapten was found to bind to the antibody. CONCLUSIONS: In the current test setting using a half-molecular analogue, it could be shown that iotrolan is probably not immunogenic. The formation of an antibody against the half-molecule coupled to bovine serum albumin can be explained only by immunogenicity of that part of the molecule, which constitutes the bridge or link to the albumin. This part of the hapten, however, is not representative of iotrolan itself.

Animals↗

Cardiac and hemodynamic tolerability of iodinated contrast media in the anesthetized rat.

RATIONALE AND OBJECTIVES: The study was designed to compare the hemodynamic effects of 11 iodinated contrast media (CM), including ionic (diatrizoate, ioxaglate), nonionic monomeric (iohexol, iopromide, iopamidol, iopentol, ioversol, iomeprol, ZK 139129), and nonionic dimeric (iotrolan, iodixanol) compounds. METHODS: Following left ventricular bolus injection of 1.2 g I/kg body weight in anesthetized rats, cardiohemodynamic parameters were measured. RESULTS: Compared with the control group, except for blood pressure (BP), all CM showed a similar response regarding the direction of the cardiohemodynamic changes after CM injection. A biphasic change in BP was observed for diatrizoate and iodixanol, whereas all other CM showed a transient increase in BP being most pronounced for ioxaglate. No arrhythmias were detected. The increase in LVEDP was lowest for the isotonic dimeric CM iotrolan and iodixanol. CONCLUSIONS: Only mild transient side effects were observed. Low osmolar, especially isotonic, dimeric CM show a clear benefit regarding cardiovascular side effects.

Animals↗