[Measurement set-up for estimation of colour discrimination thresholds of colour vision deficiencies and while wearing coloured filters]. / Messsystem zur Bestimmung von Farbunterscheidungsschwellen bei Farbsinnstörungen und unter Einfluss von farbigen Filtern.

BACKGROUND: In clinical practice, several techniques for the evaluation of colour vision deficiencies are well established. Most of them are designed for the detection of congenital or pathological changes. Due to the narrow-banded light sources, used in monitors or anomaloscopes, the human gamut can be addressed only in part. With these set-ups, the impact of coloured filters on colour vision such as blue light filtering intraocular lenses cannot be investigated precisely. MATERIAL AND METHODS: The technique is based on the visual matching of colour differences between two halves of a test field. The colours are generated by mixing seven types of LEDs. A transparent, vertically divided circular test field is retro-illuminated with this light using optical fibres and projection optics. An ocular optic assures the unaccommodated sight of the subject on the test field (size 2 degrees). RESULTS: The developed set-up presents freely adjustable colours in the form of continuous light spectra to examine the influence of filter materials on colour discrimination. A colour space can be generated which corresponds to that of human perception. The saturation and brightness of the light is adjustable. The subject has to decide if he can discriminate between the colours in the test field halves or not. Before the next colours are shown the subject is neutrally adapted by a neutral hue to provide different adaptation levels. The luminescence of the test field can be varied up to 1500 cd/m(2). The adaptive algorithm of the sequence is based on the SIAM method described by Kaernbach. Based on reference measurements, including 4 subjects with a congenital deficiency, it was shown that the discrimination thresholds at the characteristic confusing axes are significantly different than those with normal colour vision. Also, the impact of green laser goggles on the colour perception was determined. Due to the filter the thresholds in the vicinity of yellow (x = 0.4664; y = 0.4525) are reduced in the yellow-orange and cyan range and increased in the green-yellow and magenta range. CONCLUSION: With this set-up an objective instrument is available for clinical research in the field of individual human colour perception. It enables an accurate and detailed analysis of the impact of coloured filters as well as a quantitative detection of congenital anomalies. The adaptive algorithm allows short sequences and precise determination of colour discrimination thresholds.

[Effect of transparent yellow and orange colored contact lenses on color discrimination in the yellow color range]. / Einfluss transparenter gelb- und orangefarbiger Kontaktlinsen auf das Farbunterscheidungsvermögen im gelben Farbbereich.

BACKGROUND: Colored transparent filters cause a change in color perception and have an impact on the perceptible amount of different colors and especially on the ability to discriminate between them. Yellow or orange tinted contact lenses worn to enhance contrast vision by reducing or blocking short wavelengths also have an effect on color perception. METHODS: The impact of the yellow and orange tinted contact lenses Wöhlk SPORT CONTRAST on color discrimination was investigated with the Erlangen colour measurement system in a study with 14 and 16 subjects, respectively. In relation to a yellow reference color located at u' = 0.2487/v' = 0.5433, measurements of color discrimination thresholds were taken in up to 6 different color coordinate axes. Based on these thresholds, color discrimination ellipses were calculated. These results are given in the Derrington, Krauskopf and Lennie (DKL) color system. RESULTS: Both contact lenses caused a shift of the reference color towards higher saturated colors. Color discrimination ability with the yellow and orange colored lenses was significantly enhanced along the blue-yellow axis in comparison to the reference measurements without a tinted filter. Along the red-green axis only the orange lens caused a significant reduction of color discrimination threshold distance to the reference color. CONCLUSION: Yellow and orange tinted contact lenses enhance the ability of color discrimination. If the transmission spectra and the induced changes are taken into account, these results can also be applied to other filter media, such as blue filter intraocular lenses.

Effects of buffered and plain acetylsalicylic acid formulations with and without ascorbic acid on gastric mucosa in healthy subjects.

BACKGROUND: The most frequently reported adverse events associated with acetylsalicylic acid intake are minor gastrointestinal complaints. Galenic modifications, such as buffered formulations with or without ascorbic acid, may improve the benefit-risk ratio by decreasing the local mucosal side-effects of acetylsalicylic acid. AIM: To assess endoscopically-proven gastrointestinal lesions and the amount of gastric microbleeding of four different buffered and plain acetylsalicylic acid formulations, one containing paracetamol. METHODS: A randomized, four-fold cross-over study was performed in 17 healthy subjects who underwent serial oesophago-gastro-duodenoscopy before and after each course of 4-day dosing. Gastric aspirates were collected for the determination of haemoglobin concentrations to detect microbleeding. RESULTS: Buffered acetylsalicylic acid plus ascorbic acid yielded the lowest Lanza score, the lowest increase in the number of mucosal petechiae and the lowest increase in the amount of gastric microbleeding. Subjects receiving acetylsalicylic acid plus paracetamol plus caffeine showed the highest Lanza score of all treatments, and a considerably greater sum of petechiae in the oesophagus, stomach and duodenum compared with those receiving buffered acetylsalicylic acid plus ascorbic acid. CONCLUSIONS: The trial confirms that buffering of acetylsalicylic acid improves local gastric tolerability. Acetylsalicylic acid in combination with ascorbic acid shows significantly fewer gastric lesions and the lowest increase in gastric microbleeding compared with the other tested formulations.

Influence of food on the bioavailability of a carbamazepine slow-release formulation.

The pharmacokinetics of a multiple-unit carbamazepine slow-release preparation were studied after a 12-hour fast and after a standardized breakfast in 24 healthy male volunteers. There was a small increase in mean values of AUC0-infinity and Cmax when the drug was given with food. The rate of absorption of slow-release carbamazepine, as reflected by HVD, appeared to be unchanged in the presence of food. Bioequivalence was concluded for the AUC0-infinity and HVD ratios applying the inclusion rule, thus demonstrating the lack of food interaction. The results indicate that administration of the investigated carbamazepine slow-release formulation to patients in the fasting or nonfasting state seems not to be a major consideration when deciding on the regimen.

Effects of acetylsalicylic acid on ascorbic acid concentrations in plasma, gastric mucosa, gastric juice and urine--a double-blind study in healthy subjects.

OBJECTIVE: This study investigated concentrations of ascorbic acid (ASC) in gastric mucosa, gastric juice, urine and plasma in healthy subjects under steady state and fasted conditions with and without concomitant administration of acetylsalicylic acid (ASA). MATERIAL AND METHODS: This was a prospective, randomized, double-blind, parallel-group study in healthy subjects. It has assessed the effects of a 6-day administration of 0.8 g ASA or 0.48 g ASC, 3 times daily and the combination of both on concentrations of ASC in gastric mucosa, gastric juice, urine and plasma. Treatments were switched after 6 days without any washout for assessment of compartment sensitivity to changes in study medication resulting in an overall 14-day study period. Each of the 3 treatment groups consisted of 15 subjects. RESULTS: ASC concentrations were highest in the gastric mucosa (251+/-11 microg/g), followed by gastric juice (29+/-6 microg/ml), plasma (10+/-0.2 microg/ml), and urine (5+/-1 microg/ml). On day 7, ASC concentrations in gastric mucosa, plasma and urine had increased in those groups receiving ASC and decreased in the group receiving ASA only. All differences were statistically significant and indicate an interaction with ASA. In gastric juice, differences in ASC concentrations between the treatment groups were not statistically significant between baseline and day 7. ASC concentrations in plasma were strongly correlated with corresponding ASC concentrations in gastric mucosa (r = 0.34) and urine (r = 0.83), as were ASC concentrations in gastric mucosa with ASC in urine (r = 0.28). CONCLUSIONS: The gastric mucosa is the largest depot of ASC in the human body with ASC concentrations 25 times higher than in plasma. In healthy subjects, clinically relevant doses of ASA reduced ASC concentrations in gastric mucosa by about 10% within 6 days resulting from antioxidative defense mechanisms. In patients with long-term ASA treatment or conditions with additional risks such as elderly subjects with unfavorable dietary conditions and impaired antioxidative protection, a protective adjunct administration of ASC appears to be beneficial.

Lack of influence of glycine on the single dose pharmacokinetics of acetylsalicylic acid in man.

Galenic formulations consisting of acetylsalicylic acid and glycine were developed to improve solubility of the drug, even in case of ingestion without intake of water. It was the aim of this study to investigate the potential influence of glycine on pharmacokinetics after single oral administration of 1,000 mg of acetylsalicylic acid. Therefore, a bioequivalence study using a randomized crossover design (reference = without glycine, test = with glycine) in 12 healthy male volunteers (age 22 - 38 (median 26) years, body weight 64 - 83 (median 75) kg) was performed. Pharmacokinetic characteristics (AUC, Cmax, tmax, t1/2, MRT) were taken or calculated on the basis of plasma concentration/time profiles. For both acetylsalicylic acid and salicylic acid the 90% confidence intervals of the ratios of the expected median values (microT and microR) for the primary characteristics AUC and Cmax of the test and reference formulation were included in the equivalence range of 80 - 125%, which in case of multiplicative model is accepted for concluding bioequivalence. Therefore, lack of influence of glycine on the pharmacokinetics of acetylsalicylic acid including its major metabolite salicylic acid was concluded.

A scintillator-based online detector for the angularly resolved measurement of laser-accelerated proton spectra.

In recent years, a new generation of high repetition rate (~10 Hz), high power (~100 TW) laser systems has stimulated intense research on laser-driven sources for fast protons. Considering experimental instrumentation, this development requires online diagnostics for protons to be added to the established offline detection tools such as solid state track detectors or radiochromic films. In this article, we present the design and characterization of a scintillator-based online detector that gives access to the angularly resolved proton distribution along one spatial dimension and resolves 10 different proton energy ranges. Conceived as an online detector for key parameters in laser-proton acceleration, such as the maximum proton energy and the angular distribution, the detector features a spatial resolution of ~1.3 mm and a spectral resolution better than 1.5 MeV for a maximum proton energy above 12 MeV in the current design. Regarding its areas of application, we consider the detector a useful complement to radiochromic films and Thomson parabola spectrometers, capable to give immediate feedback on the experimental performance. The detector was characterized at an electrostatic Van de Graaff tandetron accelerator and tested in a laser-proton acceleration experiment, proving its suitability as a diagnostic device for laser-accelerated protons.

A dosimetric system for quantitative cell irradiation experiments with laser-accelerated protons.

An integrated dosimetry and cell irradiation system (IDOCIS) with laser-accelerated proton beams was developed, characterized, calibrated and successfully used for systematic in vitro experiments. Due to the broad exponentially shaped energy spectrum, the low-energy range of the protons (<20 MeV) and the high pulse dose, the absolute dosimetry for this beam quality is challenging. Therefore, a dedicated Faraday cup is used as an energy and dose rate independent absolute dosimeter that has been calibrated consistently with three independent methods. A transmission ionization chamber providing online relative dose information is cross-calibrated against the Faraday cup. Providing both online and absolute dose information, the IDOCIS allows for quantitative dosimetric and radiobiological studies at current low-energy laser-accelerated proton beams. Finally, first dosimetric characterizations of a laser-accelerated proton beam with the IDOCIS are presented.

[Effect of hypoxia on the relationship of density and maturity of erythrocytes of newborn, young and adult rats]. / Einfluss von Sauerstoffmangel auf die Beziehung von Dichte und Jugendlichkeit roter Blutzellen neugeborener, jugendlicher und erwachsener Ratten.

Adult male, juvenile and pregnant rats were exposed to repeated hypoxia 8 h daily for 3-9 days in a low pressure chamber (altitude of 5000 m, pO2 = 11.3 kPa and 6000 m, respectively, pO2 = 9.89 kPa). The density distribution curves of the red blood cells (RBC) and the incorporation of 59Fe into cells of different density were determined. In the ontogenesis the density of RBC increases (median density on the first day of life 1.100 kg/l; on the 21st day of life 1.102 kg/l, adult rats 1.103 kg/l). The density difference between the 1st and 4th quartile in which 50% of the cells range was 0.010 kg/l for newborn and juvenile animals and 0.004 kg/l for adult ones. Exposure to hypoxia led iN the animals of the investigated age groups to a rise of the proporborns, 0.004 for juveniles, and 0.002 kg/l for adult rats. The cumulative distribution curves of 59Fe incorporation and density of RBC can be described by the equation (formula: see text). The value alpha characterizes the relation between density, on the one hand, and the maturity and age of cells, on the other. For control and hypoxic animals the following values for alpha have been calculated: for newborns 0.515 and 0.520, for juveniles 0.829 and 0.596 (p less than or equal to 0.01), and for adult rats 0.875 and 0.823. Juvenile animals from in regard to density similar heterogenic cells as newborns after hypoxia. It may be that ontogenetically older cell forming sites or clones are reactivated.

[Relation between the density and maturity of red blood cells in the perinatal period in the rat]. / Beziehungen zwischen Dichte und Jugendlichkeit von roten Blutzellen in der Perinatalperiode der Ratte.

Relations between 59Fe incorporation into red blood cells (rbc) and their density was examined in rats during ontogenesis (20th, 21st, 22nd gestational day, 1st, 21st day of life, adults). The incorporation of 59Fe in rbc of different density was measured 24 or 96 h after application. The density separation was carried out by centrifugation of rbc in phthalate esters of known density. The density of rbc increased during ontogenesis (median density 1.093 kg/l on the 20th gestational day and 1.102 kg/l in adult rats). The erythropoietic activity, in terms of 59Fe-incorporation into peripheral rbc, is higher in newborn rats (60-70%) than in adults (30-50%). 59Fe incorporation into pregnant rats and their fetuses is similar to adult nonpregnant rats. In fetuses a relatively high incorporation of 59Fe was found in comparison to their mother. The relationship between density and maturity of rbc is postnatally more evident than in the prenatal period. (59Fe enrichment in cells of low density prenatally: 2.6 +/- 0.5, postnatally: 8.4 +/- 0.5 (1st day of life), 5.8 +/- 0.8 (21st day of life) 28.5 +/- 5.6 (adult male rats). These findings may reflect a simultaneous formation of rbc at different sites or different clonal origin during prenatal period of ontogenesis.

[Suitability of bone scintigraphy for the determination of bone reaction or regeneration following endosseous implantation of alloplastic materials with special reference to bioactive materials]. / Zur Eignung der Knochenszintigraphie bei der Beurteilug der Knochenreaktion bzw. -regeneration nach enossaler Implantation alloplastischer Werkstoffe unter besonderer Berücksichtigung bioaktiver Materialien.

A programme for the investigation of the behaviour of bioactive and bioinactive implant materials by the osseous bed was enlarged by the scanning. This one allows a follow-up of bone processes in vivo. The implants were inserted into the patellar surface of the right and left femur of rabbits. The bone regeneration after defect formation without implant serves as standard of comparison. The scintigrams were taked down with 99m-Tc-EHDP. The bone scanning provides differentiate statements about the temporal process incorporation. Its non-specificity allows no separation between the behaviour of bioactive and bioinactive materials in biologic surroundings. The scintigraphic findings can be interpreted below employment of the results of the other tests and previously known material qualities.

Scintigraphy of lymphatic vessels in malignant melanoma of the skin before operation (en bloc excision).

An injection of 99mTc-labelled antimony sulphide colloid was used to show the lymphatic pathways in patients with malignant melanoma of the trunk skin. Using a gamma camera, optimal visualisation was obtained 15-30 min postinjection. Surprising deviations of the lymphatic pathways were found; therefore, this method makes it possible to plan continuity dissection appropriate to individual cases. Two examples are presented.

[The solubility and bioequivalence of silymarin preparations]. / Untersuchungen zum Freisetzungsverhalten und zur Bioäquivalenz von Silymarin-Präparaten.

Seven silymarin products (pharmacies only), two of them with two batches each, were analysed for their ingredients, in particular silibinin (CAS 22888-70-6) and tested in vitro for their liberation of active agents. Founded on the results of these tests three products were checked for bioequivalence. Therefore, a typical phase I 3 fold crossover study was performed showing one product (Legalon) to be qualified by an approx. 2 fold higher silibinin availability compared to the two other preparations.

[A densitometric method for the assessment of myocardial perfusion using digital subtraction angiography]. / Eine densitometrische Methode zur Beurteilung der Myokardperfusion mit Hilfe der digitalen Subtraktionsangiographie.

The aim of the method presented is the quantitative description of the perfusion of the myocardium. In the framework of the invasive diagnostics of the coronary heart disease with catheterization of the left heart, ventriculography and coronarography in Seldinger's technique in 50 patients (35 of them well to be evaluated) subsequently DSA-investigations of the left coronary artery (LCA) were performed by means of the DVI-2 CV system (Philips) and densitometrically evaluated with the help of the analytic processing unit (APU). In injection by hand of 4 and 6 ml, respectively, visotrast 370 in each case 10-15 DSA-pictures in LAO 60 degrees-projection were possible. For a differentiated evaluation the total myocardium was subdivided into 12 partial areas. The densitometric analysis consisted in the calculation of time-density curves over all areas and their description by suitable parameters: density maximum (DMAX) and its moment TMAX, elevation of the curve SLOPE at 50% of DMAX, the elevation time AZEIT as well as measure for the exponential decrease of the curve after the maximum LAMBDA. For special questioning the parameters of the 12 areas were concentrated according to the main supply areas of the anterior interventricular branch (RIVA), the circumflex branch (RCX) and the apex of the heart, respectively. In the interobserver comparison the statistical analysis of the results showed deviations lower than 10% (except LAMBDA). Significant correlations were found between the body-weight and the applied quantity of contrast remedies, respectively, and the parameters DMAX and AZEIT.(ABSTRACT TRUNCATED AT 250 WORDS)

[Intraoperative detection of parathyroid tissue by semiconductor electrodes (author's transl)]. / Die intraoperative Bestimmung von Nebenschilddrüsengewebe mit Halbleiterdetektorsonden.

With miniature semiconductor electrodes of high sensitivity and special shape it is possible to charakterize diverse tissues during operation. The measured radioactivity of phosphorus reflects its enrichment and storage in the parathyroid tissue. The findings of 5 patients in whom clinically hyperparathyroidism was strongly suspected and who underwent surgery are reported. We have successfully localized parathyroidea adenomas in 3 patients, in 2 cases no adenoma could be found the storage of phosphorus 32 was normal. In all measurements we achieved a complete agreement with histological findings.

Pharmacokinetic properties of tramadol sustained release capsules. 1st communication: investigation of dose linearity.

The relationship between the dose and the pharmacokinetic characteristics. AUC(0-infinity) and Cmax was investigated with respect to linearity in 12 healthy male volunteers. Single doses of 50 mg, 100 mg and 200 mg tramadol (CAS 27203-92-5) hydrochloride were administered as sustained release capsules in an open, randomized three-period crossover study. Tramadol plasma concentrations were determined by a validated gas chromatography method. Statistical analysis after logarithmic transformation of the dose-adjusted characteristics mentioned above yielded bioequivalence for all doses applied. Therefore, dose linearity for the range investigated could be concluded.

Pharmacokinetic properties of tramadol sustained release capsules. 2nd communication: investigation of relative bioavailability and food interaction.

In an open, randomized four-period crossover study in 24 healthy male volunteers a newly developed tramadol (CAS 27203-92-5) sustained release capsule with and without concomitant food intake and an instant release formulation were administered. Additionally, a sustained release tablet was applied as further reference substance. Statistical analysis of AUC(0-infinity) and Cmax after logarithmic transformation yielded bioequivalence of tramadol sustained release capsules with and without concomitant food intake. Therefore, lack of food interaction could be concluded. The investigation also showed an only slightly diminished bioavailability of the tramadol sustained release capsules compared to the instant release formulation. Furthermore, the sustained release capsules investigated showed enhanced retardation at almost identical bioavailability compared with the sustained release competitor drug.

Pharmacokinetic properties of tramadol sustained release capsules. 3rd communication: investigation of relative bioavailability under steady state conditions.

In an open, randomized two-period crossover study in 24 healthy male volunteers multiple doses of tramadol (CAS 27203-92-5) test and reference medication were administered as follows: Test: sustained release capsules containing 100 mg tramadol hydrochloride, a total of 6 capsules at intervals of 12 h; Reference: instant release capsules containing 50 mg tramadol hydrochloride, a total of 12 capsules at intervals of 6 h. As a result of the statistical analysis of AUCss(48-72 h) after logarithmic transformation a bioavailability of 100% for the sustained release capsules compared with the instant release capsules was obtained. As expected statistical analysis of the peak trough fluctuation at steady state PTFss(48-72 h) yielded a distinct diminution of the fluctuation.