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To investigate the mechanism of interaction of gramicidin S-like antimicrobial peptides with biological membranes, a series of five decameric cyclic cationic beta-sheet-beta-turn peptides with all possible combinations of aromatic D-amino acids, Cyclo(Val-Lys-Leu-D-Ar1-Pro-Val-Lys-Leu-D-Ar2-Pro) (Ar identical with Phe, Tyr, Trp), were synthesized. Conformations of these cyclic peptides were comparable in aqueous solutions and lipid vesicles. Isothermal titration calorimetry measurements revealed entropy-driven binding of cyclic peptides to POPC and POPE/POPG lipid vesicles. Binding of peptides to both vesicle systems was endothermic-exceptions were peptides containing the Trp-Trp and Tyr-Trp pairs with exothermic binding to POPC vesicles. Application of one- and two-site binding (partitioning) models to binding isotherms of exothermic and endothermic binding processes, respectively, resulted in determination of peptide-lipid membrane binding constants (K(b)). The K(b1) and K(b2) values for endothermic two-step binding processes corresponded to high and low binding affinities (K(b1) >or= 100 K(b2)). Conformational change of cyclic peptides in transferring from buffer to lipid bilayer surfaces was estimated using fluorescence resonance energy transfer between the Tyr-Trp pair in one of the peptide constructs. The cyclic peptide conformation expands upon adsorption on lipid bilayer surface and interacts more deeply with the outer monolayer causing bilayer deformation, which may lead to formation of nonspecific transient peptide-lipid porelike zones causing membrane lysis.

In a joint retrospective study by 17 radiotherapy clinics in German-speaking countries the results of treatment of bronchial carcinoma after radiotherapy were analysed in 7503 cases. The age peak was between the 60th and 70th year. Squamous-cell carcinoma was the most frequent histological type, followed by anaplastic carcinoma, with adenocarcinoma being rare. There was a high proportion of histologically not clearly identified cases (27% in central and 35% in peripheral carcinomas). Survival rate at one year was 31% for central (3662 patients) and peripheral (961 patients) tumours, but only 2% at five years. Prognostically there was no difference between histological types and kind of radiotherapy or technique, but total dose affected survival rate. At a total dose of less than 5000 rd the survival rate at five years was minimal. The prognosis of combined surgical and radiotherapeutic measures was slightly better than with a radiotherapy alone, but results were unpredictable for the individual case. It is concluded that radiotherapy aiming at cure should be used in imoperable bronchial carcinoma if the tumour state and general condition of the patient appear to make a cure possible. But if this is not the case, radiotherapy should be used only palliatively, i.e. only to ameliorate symptoms.

Die Bedeutung der chirurgischen Therapie bei nichtepithelialen, primaren Magenmalignomen wird in einer retrospektiven Analyse an 27 Fallen untersucht. In 85,2 % der Falle handelte es sich um Non-Hodgkin-Lymphome, je 2mal lag ein Morbus Hodgkin bzw. ein Leiomyosarkom vor. Die Symptome waren uncharakteristisch und glichen denen beim Ulkusleiden bzw. beim Magenkarzinom. Die Symptom-dauer betrug durchschnittlich 6 Monate. Durch histozytologische Untersuchungen der entnommenen Probebiopsien konnte bereits praoperativ in 75 % der Falle eine richtig-positive Diagnose gestellt werden. Bei einer postoperativen Letalitat von 14,8% betrug die 5-Jahres-Uberlebensrate 56,2 % und war damit signifikant besser als die Prognose beim fortgeschrittenen Magenkarzinom.

In a joint retrospective study by 17 radiotherapy clinics in German-speaking countries the results of treatment of bronchial carcinoma after radiotherapy were analysed in 7503 cases. The age peak was between the 60th and 70th year. Squamous-cell carcinoma was the most frequent histological type, followed by anaplastic carcinoma, with adenocarcinoma being rare. There was a high proportion of histologically not clearly identified cases (27% in central and 35% in peripheral carcinomas). Survival rate at one year was 31% for central (3662 patients) and peripheral (961 patients) tumours, but only 2% at five years. Prognostically there was no difference between histological types and kind of radiotherapy or technique, but total dose affected survival rate. At a total dose of less than 5000 rd the survival rate at five years was minimal. The prognosis of combined surgical and radiotherapeutic measures was slightly better than with a radiotherapy alone, but results were unpredictable for the individual case. It is concluded that radiotherapy aiming at cure should be used in imoperable bronchial carcinoma if the tumour state and general condition of the patient appear to make a cure possible. But if this is not the case, radiotherapy should be used only palliatively, i.e. only to ameliorate symptoms.

Squamous cell carcinoma was induced in male 6 to 8-week old NMRI-mice by application of 9,10-dimethyl-1,2-benzanthracene on the skin. 15 weeks later macroscopically visible skin tumors are developed. Then organ distribution and tumor accumulation of 57Co-Bleomycin (spec. activity 1 mCi/3.3 mg) were studied 1 to 48 hours after injection. In squamous cell carcinoma a high uptake of this tumor-seeking agent can be demonstrated (n = 46). After radiotherapy (100 kV; 1.7 mm Al-filter; 18.8 Gy) (n = 26), however, a significantly reduced uptake of 57Co-Bleomycin in tumor tissue is observed. Possible consequences from these animal studies for tumor scintigraphy with this radiopharmaceutical in man are discussed.

The good response of inflammatory diseases to a low dose radiotherapy is well known. Mainly, this fact is based on experiences made in the time before antibacterial chemotherapy area. In this study our results are presented which were obtained by treating 90 patients with radiotherapy in the last years, exlusively. With respect to the end of the treatment a success rate of more than 90% was achieved. This result was compared with literature and with own findings from radiotherapy of patients with degenerative joint diseases. From the viewpoint of radio-protection the radiotherapy should be initiated as early as possible because in these cases better results could be attained at low doses. Especially, the radiotherapy of the following diseases seems to be favourable: parotitis, mastitis, abscess, furuncle, paronychia and panaritium. Besides the complications and risks of the chemotherapy the somatic and genetic radiation injuries are discussed. When radiation therapy is applied skilfully the side effects of a locally and regionally limited therapy may be neglected. It is recommended to extend the indication for radiotherapy of inflammatory diseases.

Experiments on animals are utilized for the control of hematological toxicity in sound NMRI mice during and after fractionated ICRF 159 therapy, fractionated whole-body irradiation and a combination of both. In the course of the 32-day therapeutic phase, and also during the total follow-up period lasting 196 days, continual determination of leukocytes and thrombocytes was performed. Leukocyte and thrombocyte depression is related to radiation effects during the phase of therapy and subsequently. In the later period of follow-up, however, hematological toxicity developed by ICRF 159 is higher than that produced by irradiation. Early and late effects of the preparation must be distinguished therefore. The thrombocytopenic effect is altogether less pronounced than the leukocytopenic effect. Here, too, the thrombocytopenic action of ICRF 159 appears in the course of the late phase only, but then more distinctly. The present results are discussed and compared to hitherto existing observations from animal experimentation and from clinical findings described in literature.

The importance of surgical treatment in non-epithelial, primary malignant tumors of the stomach was investigated retrospectively in 27 cases. 85.2% of these tumors were non-Hodgkin lymphomas, 14.8% were leiomyosarcomas and Hodgkin's disease. There were no typical symptoms; those present resembled the symptoms of carcinomas and peptic ulcers. Most patients showed symptoms on average 6 months prior to diagnosis. Histocytological studies of endoscopic biopsies enabled a correct diagnosis to be made preoperatively in up to 75% of cases. The postoperative mortality was 14.8%; the 5-year survival rate was 56.2%. Thus the prognosis is significantly better than that of advanced cancer of the stomach.

Radiotherapy alone is not able to improve survival time in patients with gastric cancer. Encouraged by the results of Falkson et al. [1], Moertel et al. [3], and Nordman et al. [4], we treated some patients with a combination of radiotherapy and chemotherapy in the last years.

A telecobalt therapy of lymph node groups was simulated on the Alderson phantom and the gonad dose caused by each irradiation field was measured with LiF dosimeters. When the supradiaphragmatic and the para-aortal lymph nodes were irradiated, the ovary dose showed rates up to 20% of the dose maximum. The irradiation of the same zones brought about a testicle dose of less than 50% of the dose maximum, and only 1/20 of this rate was achieved when a lead plate of about four cm was used in order to protect the testicles. The results are discussed under the point of view of the genetic risk.

In order to quantify the influence of some physical and geometrical treatment parameters on the stray radiation dose absorbed by patients undergoing radiotherapy on an 18-MeV linear accelerator, dose distributions were measured in a polystyrene phantom by means of LiF-dosimeters. For 10-MV X-rays, 6-MeV and 18-MeV electron radiation dose profiles, depth dose and isodose curves were obtained at various field sizes and treatment couch positions. By covering the phantom with 1 or 2 mm thick lead sheets a remarkable dose reduction was found. A two-exponential expression was derived to estimate stray radiation dosage in routine radiotherapy. The validity of the calculation method was demonstrated by comparing the gonadal load measured in an Alderson phantom with the calculated data.

During the establishment of a new radiooncologic department in a general hospital, a clinical tumor register has been developed for internal patient documentation. The authors describe the general requirements which had to be fulfilled by this tumor register as well as the reasons leading to the purchase of a commercial program package adapted to an irradiation planning system. The structure of the programs and the specification of characteristics are defined. Finally some aspects of organisation regarding the use of the register are mentioned.

83 patients with a benign endocrinous ophthalmopathy were submitted to radio-iodine and thyreostatic therapy and to high voltage therapy of the retrobulbar region. The ophthalmologic controls showed that 30% of the treated patients had improved data and 70% had unchanged data. These results were independent from the individual radiation qualities used and the field sizes.

The gonadal load was measured during radiation therapy of humeroscapular periarthritis, coxarthrosis, diseases of the vertebral column and of the sacro-iliac joint (disease Bechterew) for different irradiation techniques. All measurements have been performed by LiF dosimeters and with an Alderson phantom using 250 kV X-radiation. The gonadal dose with respect to the surface dose was in the range of tenths of one per mill in case of humeroscapular periarthritis and reached values up to about 30 per cent in coxarthrosis and Bechterew disease. Measurements during irradiation of the vertebral column yielded most differing values of the gonadal load depending on gonadal distances from the region exposed.

The effectiveness of radiation therapy in 233 cases with periarthritis humeroscapularis is reviewed in a prospective study from the Basel canton hospital. The patients are studied with regard to different parameters, such as duration of the anamnesis, importance of the dose, moment of evaluation of the results and influence of a 2-series technique. The total result, comprising 43.3% cases without complaints, 30.9% being better, and 25.8% whose troubles had not changed, is compared with the compiled statistical data of 4957 cases found in literature. The gonadal load is discussed on the basis of our own investigations.

The irradiation damages to the gonads caused by the radiotherapy of parotiditis and mastitis and of cheloids was determined partially under different irradiation methods. The measurements were effected with LiF dosimeters in the Alderson phantom with a tube tension of 250 kV for the inflammatory diseases and 55 kV for the cheloids. The gonad dose measured at the surface was within the range of hundreths of permille for the parotiditis, for the mastitis is was between tenths of permille and 2% depending on the therapy method. The gonad dose of the cheloid irradiations showed a clear relation to the distance between radiation source and gonads. The importance of radiological protection is emphasized.

Radiotherapy is an effective means to treat several benign diseases; in fact, the therapeutic effects set in quickly and are of a long-term nature. Relapses are rare. Side effects or other undesirable reactions are negligible. The gonads are under risk that should not be underestimated, but this is usually acceptable within reasonable limits. The age of the woman patient and localisation of the disease are decisive factors. Definite dosage reductions can be achieved by suitable radioprotective measures. Nevertheless, indications for any kind of radiotherapy with ionising radiation should be strict as a matter of principle.

In order to examine the side radiation field of X-rays from the 42-meV Siemens betatron, transverse and depth dose distributions were measured in the phantom with LiF dosemeters. The influence on the dose distribution exerted by the kind of radiation and its energy, the rotation angle of the patient's table, and the field dimensions was determined. The quality of the side radiation and the effect of additional lead shieldings were examined. The dose distributions can be calculated approximately by means of an exponent which can be used in order to estimate the surface dose for all desired irradiation conditions and to determine any distances from the field edges.

In a clinical randomized trial of 40 patients with inoperable lung carcinoma the success of radiotherapy alone (5000 rads) was compared with a combined modality with radiotherapy (5000 rads) and ICRF 159 (250 mg p.d.). There was no difference in survival rates but haematological toxicity (leucocytes, erythrocytes, platelets and haemoglobin) was marked in patients with combined treatment. In patients with oat-cell-carcinoma survival rates seem to be better after combination therapy.

The radiogenic xerostomia often poses problems to the radiotherapeutist because this symptom can become so severe that treatment has to be interrupted or in some cases even stopped. The therapeutic success can become uncertain because of such deviations from the irradiation scheme. Because of promising observations reported in literature, we have examined the stimulating effect on the salivation produced by the test preparation SL 25 from Kali-Chemie Pharma GmbH in Hannover. A double blindfold test was made. Only three out of fourteen patients (22%) in the active substance group declared to feel a relief of the xerostomia, whereas in the control group five out of twenty patients (25%) felt this relief.

A more extensive interpretation of quality control in radio-oncology is opposed to the conception mostly restricted to technical inspections. A review is given of the most important medical and physical aspects of an optimized radiotherapy. Some examples are chosen from the great number of national and international recommendations agreed upon in order to standardize the measures of quality control. Finally some simple radiobiologic models are presented and the corresponding precision requirements are compared with the uncertainties of the dose determination resulting in clinical practice.

More than 300 lymphocyte cultures of 12 patients with seminomas were examined during the prophylactic radiotherapy and, in several cases, during an extended period until 20.5 months after the end of the treatment. The object of this study was to find out by measuring the capacity of the lymphocytes to be stimulated in vitro wheather they could be damaged by the radiotherapy. Among other reasons, the above mentioned patients were chosen because they had been submitted to irradiations of vast volumes of lymphatic tissues at a uniform focal dose of 4000 rad. The different opinions expressed in the literature (stimulation decreassed resp. increased resp. unchanged) are reflected by our results in such a way that we did not find a qualitative loss of the capacity to be stimulated cultures. The problem of the different opinions about the capacity of lymphocytes to be stimulated after a radiotherapy appears; among other things, to be based on different examination methods. According to these methods- morphological determination of the relative number of lymphoblasts, synthesis of DNA by fluid scintillation counting, or determination of the number of surviving cells in vitro -different results are obtained. It seems not possible to use the lymphocyte stimulation in vitro as a method of testing clinical sideefects occuring during the characteristics of immunity and radiation biology are not differentiated in a more precise manner.