Life sciences: radiobiological advanced biostack experiment.

The radiobiological properties of the heavy ions of cosmic radiation were investigated on Spacelab 1 by use of biostacks, monolayers of biological test organisms sandwiched between thin foils of different types of nuclear track detectors. Biostacks were exposed to cosmic radiation at several locations with different shielding environments in the module and on the pallet. Evaluations of the physical and biological components of the experiment to date indicate that in general they survived the spaceflight in good condition. Dosimetric data are presented for the different shielding environments.

[Varying standard concentrations as a cause of divergent serum digoxin estimations using radioimmune-essays (author's transl)]. / Unterschiedliche Standardkonzentrationen als Ursache für divergierende Serumdigoxinbestimmungen mit Radioimmunoassays

1. The results of various commercial radio-immune essays for digoxin differ and cannot readily be compared. 2. For each RIA it is therefore necessary to determine one's own therapeutic and toxic levels in relation to the clinical requirements. 3. When quoting data, it is necessary to define the method of RIA with its therapeutic and toxic levels. 4. A cause for the high digoxin estimations of 2 RIA's carried out by the same firm has been identified as being due to the low concentration of the standard preparation. 5. The introduction of a defined and obligatory digoxin standard is recommended.

A radiopharmacological study without human radiation exposure.

The development, study and control of new drugs today is hardly conceivable without nuclear medicine studies. Nuclear physicians on ethical commissions bear great responsibility in the planning and execution of such studies. In order to protect subjects and patients those nuclear techniques are therefore to be welcome which do not include exposure to radiation. Nuclear techniques used in in-vitro diagnostics (RIA) and the determination of naturally occurring nuclides incorporated in the human body belong to this category. With the aid of a clinico-pharmacological study of a new combination of diuretics it is shown that both methods supply valuable pharmacodynamic evidence.

Embryogenesis and organogenesis of Carausius morosus under spaceflight conditions.

The influence of cosmic radiation and/or microgravity on insect development was studied during the 7 day German Spacelab Mission D1. Eggs of Carausius morosus of five stages differing in sensitivity to radiation and in capacity to regeneration were allowed to continue their development in the BIORACK 22 degrees C incubator, either at microgravity conditions or on the 1 g reference centrifuge. Using the Biostack concept--eggs in monolayers were sandwiched between visual track detectors--and the 1 g reference centrifuge, we were able to separate radiation effects from microgravity effects and also from combined effects of these two factors in space. After retrieval, hatching rates, growth kinetics and anomaly frequencies were determined in the different test samples. The early stages of development turned out to be highly sensitive to single hits of cosmic ray particles as well as to the temporary exposure to microgravity during their development. In some cases, the combined action of radiation and microgravity even amplified the effects exerted by the single parameters of space. Hits by single HZE particles caused early effects, such as body anomalies, as well as late effects, such as retarded growth after hatching. Microgravity exposure lead to a reduced hatching rate. A synergistic action of HZE particle hits and microgravity was established in the unexpectedly high frequency of anomal larvae. However, it cannot be excluded, that cosmic background radiation or low LET HZE particles are also causally involved in damage observed in the microgravity samples.

Influence of cosmic radiation and/or microgravity on development of Carausius morosus.

Eggs of Carausius morosus were exposed to spaceflight conditions in two spaceflight missions, the German 7 day Spacelab Mission D1 and the Soviet 12.56 day Biosatellite Mission "COSMOS 1887". During spaceflight the eggs continued their development. Eggs of five different ages representing different sensitivity to radiation and different capacity to regeneration were used to investigate the influence of cosmic radiation and/or microgravity on insect development. Using the Biostack concept--eggs in monolayers sandwiched between nuclear track detectors--and the 1 g reference centrifuge of BIORACK in D1 we were able to separate effects of heavy ions of the cosmic radiation from microgravity effects and also from combined effects of these two factors in space. After retrieval, hatching rates, embryonic and larval growth kinetics and anomaly frequencies were determined. Microgravity leads to a reduced hatching rate of eggs exposed in the early stages of development. Hatching was normal in eggs which were exposed on the 1 g reference centrifuge. Hits by heavy ions caused body anomalies. The combined action of heavy ions and microgravity resulted in an unexpectedly high frequency of anomalies. These results obtained from the Spacelab Mission D1, were confirmed in an experiment onboard of COSMOS 1887. In addition to the previous analysis, embryonic development before hatching was followed which showed no major difference between flight and the ground control specimens. Since a reconfirmation of reduced hatching rates was observed in COSMOS 1887, too, the above results suggest some microgravity induced functional impairment of the hatching activity, rather than blockage in embryonic development.

Advanced biostack: experiment 1 ES 027 on Spacelab-1.

The radiobiological properties of the heavy ions of cosmic radiation were investigated on Spacelab 1 by use of biostacks, monolayers of biological test organisms sandwiched between thin foils of different types of nuclear track detectors. Biostacks were exposed to cosmic radiation at several locations with different shielding environments in the module and on the pallet. Evaluations of the physical and biological components of the experiment to date indicate that in general they survived the spaceflight in good condition. Dosimetric data are presented for the different shielding environments.

[Nuclearmedical tumor diagnosis]. / Nuklearmedizinische Tumorsuche.

Nuclear medicine diagnosis is an important discipline in cancer searching. By using reliable radiopharmaceuticals practically all organs can be investigated, especially bone cancer.

[Sources of error in the radioimmunochemical determination of digoxin in serum]. / Fehlerquellen bei der radioimmunochemischen Digoxinbestimmung im Serum

In a study with numerous samples of serum we compared 5 Digoxin RIA and evaluated the reliability of tests by simultaneous determinations. There were found considerable differences in the determinations with the various RIA for the same serum; evident differences also were recorded in the recovery and in the reproducibility of the assays. Among some other sources of error the dependence of temperature and of the duration of the dextran-charcoal separation were observed; therefore, the charcoal incubation is recommendable at 4 degrees C. Each laboratory which is able to perform the determinations of digoxin concentrations in the serum should declare its own range for the therapeutic and toxic levels for the used RIA in collaboration with the clinicians.

[Distribution of 4-14C-mofebutazone in the rat]. / Zur Verteilung von 4-14C-Mofebutazon bei der Ratte.

To further elucidate the distribution and differentiation of mofebutazone in comparison to phenylbutazone, 6 rats received 200 mg/kg 4-14C-mofebutazone corresponding to approx. 27 microCi/animal. 2 animals were sacrificed each time after 45 min, 6 h and 24 h. The 4-14C-plasma level was determined at the corresponding test periods and the radioactivity eliminated within 24 h in the urine was also determined. In addition autoradiograms of the whole animal were prepared for each animal. According to this study 4-14C-mofebutazone is distributed mainly in the metabolisation and elimination organs, a moderate activity was to be found under the skin and muscle tissue, but none, however, in the central nervous system and the bone marrow. Nearly 81% of the substance was eliminated after 24 h and with exception the colon the corresponding autoradiograms were practically free of activity. Because of the short half-life time and the rapid elimination mofebutazone does not lead to any accumulation.

Dose-dependent pharmacokinetics of dexamethasone.

The dose dependency of the pharmacokinetics of dexamethasone and its influence on the endogenous secretion of cortisol has been studied in healthy females. The maximum plasma level occurred between 1.6 and 2.0 h after doses of 0.5-3.0 mg independent of the type of administration. AUC, distribution volume, plasma clearance and cmax did not increase in proportion to the dose but only by the factor of about 0.6-0.7 after the oral administration of 0.5-1.5 mg. Comparatively high values were reached after 3.0 mg i.m. This may be due to reduced bioavailability of the oral doses. Within the first 12 h after the administration of 0.5-3.0 mg, endogenous cortisol secretion was influenced independent of dose. However, the suppressive effect after 24 h was dose dependent and amounted to approximately 24% for 0.5 mg p.o., 62% for 1.5 mg p.o. and 90% for 3.0 mg i.m. In the case of administration every second day, the integral reduction within 24 h after the administration of 0.5 mg dexamethasone was 44 to 65% and for 1.5 mg between 59 and 62%.

[Serum dixogin determination. Clinical significance, results and error consideration based on comparative studies with different radioimmunoassays]. / Digoxinbestimmung im Serum. Klinische Bedeutung, Ergebnisse und Fehlerdiskussion an Hand vergleichender Untersuchungen mit verschiedenen Radioimmunoassays

In order to compare 5 different radioimmunoassays (RIA's) and their results we determined the digoxin concentration in the serum of 186 patients and point out some sources of error. We consider the following points important: 1. There were found varying results in the determination of digoxin concentration in patient's sera using different RIA's. 2. One of the essential reasons for these differences are discrepancies of the RIA standards which belong to each kit. 3. It should be required that the control standard is equal to all RIA's. 4. Each laboratory which carries out digoxin determinations should, in collaboration with the clinic, work out and announce its own guide-line values for the RIA used in regard to the optimal therapeutic range and also to overdoses.

[Technical organisational problems and development tendencies in medical data processing (author's transl)]. / Technisch-organisatorische Probleme und Entwicklungstendenzen in der medizinischen Datenverarbeitung

All uses of "Medical Data Processing", which make greatly divergent demands on the computer because of the different applications by different user groups, are to be considered from the points of view of hardware, software and organisation. Further possibilities for the complex information systems in the hospital arise from the more recent development of computer technology, also with regard to the reliability of the hardware. Hand in hand with this, an improvement in the system software can be seen for the real-time processing and time sharing. But organisation od design, planning, installation and operation is of particular importance for medical information systems. This also includes the preparatory training of the hospital personnel and the observance of data protection.

RBE values for fast neutrons in connection with estimates of the radiation burden in space.

Much data concerning radiation in space as a serious danger to astronauts can be obtained in laboratories on Earth. For different parameters we investigated the relative biological efficiency (RBE) of 14-MeV neutrons on mice, rats and guinea pigs (being wholly exposed). Also the mitosis inhibition for isolated cells was determined. The RBE values found were: for lethality in the LD50(30d)-region--about 2 (for mice, rats and guinea pigs); for reduction due to radiation of living weight of different animals--2 to 3; for reduction of small gut weight of rats and guinea pigs--2.5 and 2; for histological changes in blood and albumin serum (rats and guinea pigs)--about 2; for the highly sensible cells of the lense epithelium from eyes of rabbits--2.5; for the mitosis inhibition of HeLa cells--2.5. The apparatus for radiation tests is described and measuring methods are indicated. The radiation of the whole body of mice, rats and guinea pigs was determined by activating of MgCl2 solution filled into phantoms. By means of a computer, the depth-dose curve can be determined for larger biological objects.

[Therapy of heart failure with combined furosemide retard/triamterene]. / Therapie der Herzinsuffizienz mit der Kombination Furosemid retard/Triamteren.

20 patients with an average age of 73.3 years suffering from left cardiac insufficiency in stage II to III of the NYHA, who could not be recompensated alone by means of digitalisation, received additionally the diuretic combination furosemide-retard (30 mg)/triamterene (50 mg) for 2 to 3 weeks. Subjective side effects were not observed. The laboratory parameters did not show any substantial changes. A short increase of uric acid and serum creatinine in the older patients returned to normal spontaneously. A decreased potassium level returned to normal; a hyperkaliemia was not observed. The repeated administration of the combination did not lead to any accumulation; only a balanced concentration at a low level appeared. The urine elimination, the decrease in body weight, the regression of the lung congestion and the size of the heart were statistically significant.

[Pharmacology, toxicology and pharmacokinetics of mofebutazone]. / Zur Pharmakologie, Toxikologie und Pharmakokinetik von Mofebutazon.

The difference between mofebutazone and phenylbutazone is shown by means of toxicological, pharmacological and pharmacokinetic studies as well as by the protein binding. In spite of a certain chemical similarity both substances differ distinctly. Mofebutazone is approx. 5-6 times less toxic than phenylbutazone but its analgesic and antiphlogistic effects are weaker than those of phenylbutazone. The half life time of mofebutazone of 1.9 h is considerably shorter than that of phenylbutazone (54-99 h). Mofebutazone, in contrast to phenylbutazone, is mainly glucuronidised and to 94% eliminated within 24 h, phenylbutazone on the other hand to only 88% within 21 days. In spite of a high plasma protein binding quota of 99%, mofebutazone is classed among those substances with a medium binding potential. Conclusions may only be drawn with great reservation with regard to a category of substances from the effect and side effects of one substance on the basis of the present studies.

Measurement of theophylline absorption from different regions of the gastro-intestinal tract using a remote controlled drug delivery device.

The absorption of a theophylline solution containing 80-120 mg doses delivered to different sites in the gastro-intestinal tract has been determined in 3 male volunteers using a remote controlled drug release system (HF-capsule). There was no difference between the stomach, ileum and the colon in the amount of theophylline absorbed (AUC). The T 1/2abs of theophylline absorbed via the colon was prolonged when compared with that entering via the upper gastro-intestinal tract. The results provide a rational basis for the further development of theophylline formulations and are indispensable for planned development and to account for variation in the bioavailability of retarded release drug preparations.

Preliminary results on the action of cosmic heavy ions on the development of eggs of Artemia salina.

The Biostack experiment (Principal Investigators: H. Bucker) aboard Apollo 16 contained one unit with eggs of the brine shrimp Artemia salina. The eggs were fixed in polyvinyl alcohol foils. Nuclear emulsions and plastics were used as track detectors. The development of 260 eggs hit by cosmic heavy ions was investigated. It differed significantly from the development of the flight controls--eggs flown in the Biostack but not hit by heavy ions--and of the ground controls. From these results it was concluded that a hit of a single heavy ion may injure the encysted blastula. This damage was found to influence the gastrula formation and even the hatching process of the nauplius. Abnormalities of the orthonauplius were observed during the development of the hit eggs. These are shortened extremities, or abnormal thorax or abdomen. In addition, in the Biostack II aboard Apollo 17 eggs of Tribolium confusum and Carausius morosus were included. The influence of single heavy ions on the development process of these highly organized insects was investigated.