[Who is responsible for pain therapy?].
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Biomedical subjects
Publications and source records attributed to K Hempel.
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The frequency of H-2Kk and HPRT-deficient T cells was measured in the H-2Kb, kDd,k genotype mouse 8-10 weeks after X-ray exposure at doses up to 6 Gy to compare the mutant frequency (MF) of an autosomal gene with that of an X-chromosomal gene. H-2K mutants were enriched by magnetic cell separation (MACS) using the H-2Kk-specific monoclonal antibody H100.5/28 and were isolated by limiting dilution cloning. Finally, the mutant phenotype was verified by flow cytometric analysis in a representative number of clones. The frequency of HPRT-deficient T cells rises from 2.5 x 10(-6) at 0 Gy to a maximum of 1.13 x 10(-4) at 4 Gy, and decreases to 2.9 x 10(-5) at 6 Gy. The H-2K- MF in the non-irradiated mouse was 8.4 x 10(-7). It increases with dose to a maximum of 8.1 x 10(-6) at 4 Gy and declines to 3.3 x 10(-6) at 6 Gy. The H-2K- MF measured depends on the monoclonal antibody used for the isolation of mutants. In a pilot study with another H-2Kk-specific monoclonal antibody (11.4.1), the spontaneous MF was four times higher than in experiments with the H100.5/28 monoclonal antibody. The expression of other class 1 antigens was investigated in H-2K- clones. The H-2Dd antigen had also disappeared in six of 41 clones from irradiated animals. This gene is situated at a distance of 1500 kb from the K-locus. The H-2Kb antigen was present in every investigated clone. In the discussion a model is presented that explains the shape of the dose-response curve of MF by selection against mutants in vivo systems under homeostasis. The results of the present investigation indicate that observed X-ray mutagenicity depends on many factors and that several genes have to be explored before reliable risk estimates are possible.
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One of the most important intentions of GSG 1992 is the favourization of traditional ambulatory surgery by legislative measures. However in general surgery a much higher potential for a significant reduction in cases of classical hospitalization and thus concomitant substantial financial savings lies in short-stay eg. one-day/one-night procedures. At present methods of laparoscopic cholecystectomy, thyroid surgery and herniorrhaphy-together about 50% of common hospital patients-are developed enough to be practiced safely under this strategy. In the future further suitable techniques could evolve from minor access surgical concepts.
The limitations of each specialty are laid down in the rules for continuing education for physicians. The necessary cooperation between the surgeon and the anesthesiologist is discussed on the example of the polytraumatized patient and the pain therapy after surgery. All rights and duties of the emergency team have to be laid down by the hospital management. The medical responsibilities for the therapeutic actions are on the side of the specialists.
A method is described for determining the frequency of cells with a mutation in an autosomal gene coding for a membrane protein. Using a monoclonal antibody to H-2Kk surface antigen and magnetic cell separation (MACS) more than 10(4)-fold enrichment of the H-2Kk negative population was achieved, as tested with artificial mixtures containing a known number of antigen-negative cells. After a second magnetic sorting mutant frequencies as low as 10(-6) could be measured. The number of clonogenic mutants was evaluated by limiting dilution cloning and verification of the mutant phenotype by FACScan (flow cytometry) analysis in a representative number of clones. The spontaneous frequency of H-2Kk deficient mutants was 0.80 x 10(-6), and this increased after irradiation with 6 Gy X rays to 3.38 x 10(-6) within the next 8 weeks. About 50 mutant clones were screened for the presence of other class 1 antigens on the cell surface by FACScan analysis. All mutants continued to express other class 1 antigens.
From 1983 to 1990, 82 knee arthroscopies (8.2%) carried out in our patients found nothing pathological. Sixty-four percent of these patients were active in sports, but trauma was noted in 32% of the cases only. Football and other ball games, skiing, and track and field athletics were the main causes. Twenty-six percent of the patients had undergone previous surgery in the affected knee. At a mean of 4.6 years postoperatively, clinical and radiological re-assessment was conducted so as to compare our pre- and intraoperative findings with the further course of events. We found that 48.2% of the patients were symptom-free after the diagnostic arthroscopy, 37.5% had persistent discomfort and 14.3% had a recurrence of discomfort after 6 months to 2 years. The objective measurement score (Zarins Rowe score), at 47.5 out of 50 points, was better than the subjective score, at 40 out of 50 points. Our diagnoses had to be changed retrospectively: meniscal lesions were diagnosed too frequently, while chondropathia patellae and instability were often missed. Additionally, complaints could be related to abnormal axis, limited range of motion of the hip or knee, leg length inequality and hypermobility. Being unable to verify a presumed intra-articular lesion arthroscopically is frustrating for both doctor and patient. Our data suggest that meniscal signs should be looked at more critically and emphasise the need for a complete evaluation of the whole locomotor system.
The frequency of hypoxanthine phosphoribosyl transferase (HPRT) deficient splenic T lymphocytes was measured in the 137Cs gamma-irradiated mouse by the T cell cloning method. Doses from 0.3 to 6 Gy were applied at the dose-rates 0.5 Gy/min, 1 Gy/day and 1 Gy/week. Mutants were determined 8-10 and 30-40 weeks after the end of exposure. Radiation-induced mutant frequency (MFi) was calculated by subtracting the age corrected spontaneous mutant frequency (MFsp) from total mutant frequency (MF) found in irradiated animals. Data were fitted to linear and linear-quadratic dose-response models. MFi depended markedly on dose, dose-rate and time after exposure. When mutants were determined 8-10 weeks after acute irradiation (0.5 Gy/min) the dose-effect curve fitted the linear-quadratic equation MFi = 6.9 x 10(-6) Gy + 1.2 x 10(-6) Gy2, whereas in low dose-rate experiments (1 Gy/day, 1 Gy/week) the dose-effect curves were linear. The slope of the linear regression was about 3 x 10(-6). When low dose-rate-irradiated animals were killed 30-40 weeks after irradiation, MFi was about one-third of that observed after 8 weeks. The dose dose-rate effectiveness factor (DDREF) for radiation mutagenicity was calculated in animals that had been exposed 8-10 weeks previously. For doses < 2 Gy the reduction in effectiveness was about 1.5 when the irradiation dose-rate was < or = 1 Gy/day. For higher doses DDREF was 3-5.
BACKGROUND: Cryopreservation of erythrocytes using hydroxyethyl starch (HES) as cryoprotecting additive could result in a nearly unlimited storage stability of preserved red cells. In addition, it would allow its immediate use for transfusion. In order to assess the therapeutic efficacy of erythrocytes cryopreserved with HES, their 24-hour post-transfusion survival and long-term survival was evaluated. MATERIALS AND METHODS: The experiments were carried out with dog erythrocytes as an animal model for human erythrocytes. To each of 6 German shepherd dogs a 15-ml sample of erythrocyte suspension, labeled with 51Cr (25 microCi) after thawing, was autologously injected. Caused by hemolysis 29% of the formerly cryopreserved erythrocytes have not been labeled. To each of 6 control animals 15 ml of a suspension of freshly drawn and 51Cr-labeled erythrocytes was injected. The 51Cr radioactivity in later taken blood samples was a measure for the number of injected erythrocytes having remained in the circulation until the moment of blood withdrawal. The effect of cryopreservation was assessed by comparison of the test group with the control group. RESULTS: In both groups 30% of the applied cells left the circulation within 30 min. This was effected by pharmacological enlargement of the dogs' spleen and not by hemolysis of the erythrocytes. After the first 24 h all of the cryopreserved labeled erythrocytes had survived to the same amount (> 95%) as the labeled fresh red cells. Between 12 h and 20 days after injection, in both groups the 51Cr activity decreased exponentially by 4.8 and 4.5%/d. This difference was not significant. The area under the curve amounted to 1253 and 1257% d, respectively. CONCLUSIONS: There exists a subpopulation of red cells that is destroyed by freezing stress. As a result the freed stroma would be a serious transfusion risk. All erythrocytes having survived the cryopreservation procedure resemble the fresh erythrocytes with regard to the in-vivo survival; their therapeutic efficacy is not impaired. In the context of in-vitro results with human erythrocytes it can be expected that at the present developmental state of the cryopreservation procedure at least 93% of the human erythrocytes cryopreserved with HES have a normal 24-hour and long-term post-transfusion survival.
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The effect of Combolen (3.9 mg/kg bw s.c.) on the distribution of erythrocytes in dogs was investigated. After application of Combolen, the hematocrit of the animals decreased exponentially within 1 h by 21%. The reversal of the reduction began from 2 h after the time of application, amounting to 4% within the first day and finishing by the fourth day. After injection of 51Cr-labelled erythrocytes, radioactivity in the circulation of Combolen-treated dogs decreased exponentially within 2 h by at least 30%. It was concluded that the dog's spleen, under physiological conditions, contains about 10% of the animal's blood. The time-courses of the decrease of hematocrit and radioactivity in the circulation were found to be very similar. In accordance with this observation, a high correlation (r = 0.97) between the level of radioactivity after injection of radio-labelled erythrocytes and the corresponding hematocrit values after application of Combolen was found. After application of erythrocytes, labelled with 99mTc, an extensive distribution from the circulation into the spleen was observed by scintigraphy. This process can be understood by using a closed-compartment model. An equation, based on this model, describes the observed time course of the hematocrit values, as well as the number of 51Cr-labelled erythrocytes, in Combolen-treated dog. Presumably, the observed effect of Combolen is the result of the relaxation of the smooth muscle cells in the trabeculae of the spleen, caused by central-nervous depression of sympathetic tone. Combolen seems to be a suitable tool in pre-clinical testing of a novel blood preserve with dog as a test animal. Its potent ability to eliminate erythrocytes from circulation is distinguishable from the sequestration of damaged red cells. Furthermore, its ability to prevent the spleen from uncontrolled hematocrit modulating actions in addition to its sedative effects is considered to be an invaluable advantage.
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The in vivo effect of exogenous vasoactive intestinal polypeptide (VIP) on the accumulation of cAMP in 21 microdissected brain nuclei was investigated 3 and 7 min after intraventricular injections in rats. VIP elicited significant (up to 20-fold) increases in cAMP levels. This effect is region specific varying considerably among the brain regions investigated. VIP dramatically increased the cAMP content of the lateral septal nucleus, several hypothalamic nuclei, the habenula, the midbrain central gray and the locus coeruleus. Smaller increases were observed elsewhere including some VIP-rich brain areas such as the cerebral cortex and the hippocampus.
In radiobiology the reduction of the dose-rate in general diminishes the degree of the biological effect per unit dose. This phenomenon is characterized by the dose-rate effectiveness factor (DREF). DREF is the factor by which a risk per unit dose obtained from data at high dose and high dose-rate overestimates the risk at low doses and/or low dose-rates. In general, DREF is in the range of 2 to 10. In the first part of this review, a short survey of the modern microdosimetric approach for a better understanding of radiation load on the cellular level and the significance of dose-rate is given. Experiments on the influence of dose-rate on the mutagenicity of ionizing radiation in cultured cells are reviewed. In contrast to other biological effects, in most experiments the reduction of the dose-rate had no or even a reverse dose-rate effect (DREF < or = 1). In the second part results on the influence of dose-rates on the induction of HGPRT-deficient T-lymphocytes in mice irradiated in vivo are given. Mutagenicity decreases with dose-rate and DREF values between 3-10 were measured. Possible reasons for the discrepancy between in vitro and in vivo experiments are discussed.
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