[Esophageal carcinoma: the final results of a multicenter and controlled German study with misonidazole and radiation]. / Osophaguskarzinom: Endergebnis einer multizentrischen und kontrollierten deutschen Studie mit Misonidazol und Bestrahlung.

A prospective, randomized clinical study on 91 patients with squamous cell carcinoma of the oesophagus was undertaken in order to investigate the radiosensitizing effect of misonidazole. After histologic verification and extensive diagnosis, the greater tumor region was at first irradiated during 2.5 weeks with ten fractions of 3 Gy each up to a target volume dose of 30 Gy. Prior to each fraction, patients received randomly misonidazole or a placebo in a dose of 1 g/m2 body surface. Then they were presented to the oncologic surgeon in order to decide whether a surgical resection should be performed or not. Following to this operation no further radiotherapy was performed. However, if a surgical intervention did not take place, radiotherapy was continued without administration of misonidazole or placebo up to a target volume dose of 60 to 70 Gy. There was no evidence of neurotoxic side effects or modifications of the blood count and some laboratory parameters caused by misonidazole. As to recurrence-free interval and survival time, no significant differences were found between the different therapy groups, so that a radiosensitizing effect of misonidazole was not demonstrated in this study. Regarding several positive phase II studies with misonidazole, some hopes had been placed in this study because at present the therapeutic situation in oesophagus carcinoma is extremely unsatisfactory. Even the combination of a most sophisticated operation technique prior or following to irradiation could not essentially improve the poor healing rates.

[Radiotherapy of cervix and uterus carcinomas (Marburg results of 1960 to 1975)]. / Beitrag zur Strahlentherapie der Kollum- und Korpuskarzinome (Marburger Ergebnisse 1960 bis 1975).

The authors present the therapy results and complications of 479 patients with carcinomas of the cervix and 241 patients with carcinomas of the body of the uterus. The five-year survival rate of the patients with carcinomas of the cervix is 57%. The first five years after diagnosis were survived by 79.6% of the patients in stage I, 57.3% of the patients in stage II, 31.1% of the patients in stage III, and 5.9% of the patients in stage IV. 60% of these patients were only submitted to percutaneous and intracavitary irradiation, and 40% were irradiated after operation. The five-year survival rate of the patients with carcinoma of the body was 74.3%. This rate was 80.8% in stage I, 77.5% in stage II, 57.5% in stage III, and 30% in stage IV. The operation frequency was relatively high with 74%, only 26% of these patients were only treated by radiotherapy. The percutaneous radiotherapy was performed exclusively under high voltage conditions, preponderantly according to the method of Marburg which allows a homogenous, small-field irradiation of the small pelvis with a dose until 45 Gy, but which deliberately does not expose to radiation the para-aortal lymph nodes. In the years of 1966 to 1971, a comparison with the method established in Düsseldorf was made. This method is working with two big U-shaped stationary fields including the para-aortal lymph nodes. The central part of the pelvis is collimated when percutaneous irradiation is applied, and the intracavitary treatment is applied with a higher dose, correspondingly. The present analysis of the treatment results of both methods does not show any significant difference as to the survival time. The incidence of fistulas, however, a severe late complication, which is 2.4% for the method of Marburg, is markedly lower than that of 8.6% for the other method. Prognostic factors and therapeutic aspects are discussed in detail.

Treatment of penis carcinoma.

Amputation of the penis is by no means the quickest and least invasive of the surgical methods of treating penis carcinoma. Radiation therapy has the advantage of preserving the integrity of the penis and does not render a later operation of the penis impossible. Regional lymph node metastases should be removed surgically whenever possible; their radical extirpation, especially total lymphadenectomy, should not be too vigorous because it is essential to avoid any complications, and irradiation of the inguinal and iliac lymph node regions by modern methods of radiation therapy is acceptable to the patient and can still be helpful even in more advanced cases. We do not yet have enough experience with cytotoxic therapy, bleomycin or laser coagulation to alter our present method of treatment.

[Heart function during postoperative high-voltage therapy in female patients with left-sided breast cancer]. / Die Funktion des Herzens unter postoperativer Hochvolttherapie bei Patientinnen mit linksseitigem Mammakarzinom.

Systolic time intervals according the method of Weissler were measured in nine females (mean age: 55.1 years) with mammary carcinoma on the left, prior to, during and 3 months after postoperative radiation therapy. The average load to the anterior cardiac wall amounted to 36 Gy. We found a reversible statistically highly significant decrease of left ventricular function (increase of PEP/LVET) during radiation therapy, which seems to be related to a radiation-induced acute pancarditis known from animal experiments.

[An electrocardiographic study of cardiac damage following post-operative radiation in patients with mammary carcinoma on the left (author's transl)]. / Elektrokardiographische Untersuchungen zur strahleninduzierten Kardiomyopathie bei Mammakarzinom-Patientinnen während postoperativer Hochvolttherapie.

Systematic ECG-analysis were performed in 13 patients (mean age 55.1 years) with mammary carcinoma on the left, prior to, during, and 4 months after postoperative radiation therapy. Treatment was done with a gammatron, the average load to the anterior cardiac wall amounted to 36 Gy. All patients exhibited ST-T segment changes, flat, isoelectric or coronary negative T-waves in the precordial leads demonstrating radiation-induced perimyocarditis. Prolongation of QT-interval corrected with Bazett's formula (QTc) was observed in 6 patients showing myocardial damage. Sinus tachycardia in 9 patients and lower voltage in 3 patients gave a hint to early appearance of pericardial effusions. Pulmonary P-waves in 6 patients and shift of QRS-axis to the right in 5 patients demonstrated early damage of the right heart. Clinical deterioration could not be seen in any patient.

[Concentration of neuraminic acid in the serum of tumor patients (author's transl)]. / Neuraminsäure-Konzentration im Serum von Tumorpatienten.

The neuraminic acid level in the serum of 588 patients was determined. The patients suffered from bronchial carcinomas other malignant diseases (mastocarcinoma, carcinoma of the cervix and the body of the uterus, Hodgkin's lymphoma, non-Hodgkin's lymphoma), and benign pulmonary diseases (tuberculosis of the lungs and chronic obstructive pulmonary diseases). The average level of 162 patients with bronchial carcinomas is 3,449 mumol/ml of serum; thus it is significantly higher than the average level of 98 sound control persons (2,336 mumol/ml) and 88 patients with benign pulmonary diseases (2,733) mumol/ml). The other patients with malignant diseases also presented an increased concentration of neuraminic acid in the serum, however, this increase was not as significant as for the patients with bronchial carcinomas. The possible role of neuraminic acid as biological "marker" is discussed.

[ECG-changes following postoperative irradiation of patients with mammary carcinoma (author's transl)]. / EKG-Veränderungen nach postoperativer Bestrahlung von Mammakarzinom-Patientinnen.

Systematic ECG-analyses and determinations of serum creatin-kinase were performed in 32 patients with mammary carcinoma of the left, prior to and immediately after postoperative radiation therapy. Treatment was done with a gammatron, during this, the average load to the anterior cardiac wall amounted to 3600 rd. Eleven cases exhibited coronary-negative T-waves in at least two chest leads after treatment, seven other cases had flat negative or isoelectric T-waves. Two patients additionally revealed prolongation of the relative QT-period by more than 115%. These changes are interpreted as a sign of radiation-induced myopericarditis. Pericardial effusions did not appear during the follow-up period, furthermore no modifications of creatin-kinase activity. Clinical injury to the patients developed in no case.

[Combination chemotherapy in patients with disseminated bronchogenic carcinoma (author's transl)]. / Kombinationschemotherapie bei Patienten mit metastasiertem Bronchialcarcinom.

49 patients with disseminated bronchogenic carcinoma (small cell, 16;squamous cell, 17;large cell, 12;adeno, 4) were treated with a combination of adriamycin, cyclophosphamide, vincristine and DTIC. In a randomized series (21 patients) chemotherapy alone was compared to chemotherapy plus heparin. Partial remission was achieved in 8 patients with small cell carcinoma, in 5 patients with large carcinoma and in 2 patients with squamous cell carcinoma. The survival of patients who responded to therapy was greater than the survival of patients who did not respond to therapy. The duration of remission and the survival time was not longer in patients who had additional heparin therapy.

[Influence of roentgen rays on electrolyte changes and metabolism of the myocardium. VII. Radiation-induced inhibition of the sodium- and potassium--activated microscomal-trasport ATPase]. / Untersuchungen über den Einfluss von Röntgenstrahlen auf Elektrolytverschiebungen und Stoffwechsel des Herzmuskels. VII. Strahlenbedingte Hemmung einer Na+- und K+-aktivierbaren mikrosomalen Transport-ATPase

The behavior of a Mg2+-dependent microsomal ATPase, which may be activated by Na+ and K+, was investigated in the myocardium of Guinea pigs after local irradiation. The part which can be activated by Na+ and K+ (transport-ATPase) is already slightly inhibited thirty minutes after a dose of 250 R; the inhibition rate with 1500 R amounts to about 60%, the maximal inhibition effect with a dose of 3000 R was about 70%. Four hours after a local irradiation with 1500 R, a restitution of the inhibition effect occurs with overshoot reaction; 15 and 24 hours following irradiation, a significant inhibition of the transport-ATPase activity can again be verified. The k-strophanthidine and digitoxin are inhibiting within the concentration ranges analyzed (2 X 10(-5), 2.5 X 10(-7), 5 X 10(-7) M) the activity of the transport-ATPase. The above-mentioned radiation-induced inhibition effect upon the ATPase activated by Na+ and K+ is additively increased by adding k-strophanthidine (2 X 10(-5) M) and digitoxin (2.5 X 10(-7) M).

[Studies on the bioavailability of the individual components from a combination of dilazep and beta-acetyldigoxin (author's transl)]. / Uber die Bioverfügbarkeit der Einzelkomponenten aus einer Kombination von Dilazep und beta-Acetyl-digoxin

Original tablets of Cormelian [= 50 mg 1,4-bis[3-(3,4,5-trimethoxybenzoyl-oxy)-propyl]-perhydro-1,4-diazepine (dilazep)] and Cormelian-Digotab (= 50 mg dilazep + 0.2 mg beta-acetyl-digoxin) were produced with 3H-dilazep as prescribed in the special galenic technique. After application of a single oral dose of two tablets dilazep to 9 patients serum concentration was analysed at different times up to 24 h p.a.; the renal excretion rate of dilazep and metabolites was determined up to 48 h. Two tablets of the combination were given to 4 of these patients 4 days after application of dilazep and the corresponding analysis were repeated; in the serum of these patients the concentration of glycoside was determined by radioimmuno assay. The following results were obtained. 1. Differences in serum concentrations and renal excretion rates of dilazep and metabolites were not observed after application of the mono- and combination product. In comparison to results after oral application of pure dilazep in gelatin capsules the serum concentrations 1 h after application of Cormelian and Cormelian-Digotab were statistically significantly higher. With reference to comparable total absorption rates these results may be representative for a possibly retarded absorption rate of dilazep given as pure substance. An influence of the different galenic techniques on the intensity and direction of metabolites could not be substantiated. 2. By large dispersions of the single values high absolute and relative concentrations of beta-acetyl-digoxin were found in the serum of all the 4 patients after application of combination. Contrary to two commercial products, applied to each of 10 test persons under comparable conditions, statistically higher serum concentrations of glycoside were analysed 1 h after application of the combination. The results of these studies confirm a positive influence of the galenics on the biological availability of both the components in the combination drug Cormelian-Digotab.

[Effect of x-rays on changes in electrolytes and metabolism of the myocardium. VI. Radiation-induced changes of catecholamine content]. / Untersuchungen über den Einfluss von Röntgenstrahlen auf Elektrolytverschiebungen und Stoffwechsel des Herzmuskels. VI. Strahlenbedingte Veränderungen des Katecholamingehaltes

In the myocardium of guinea-pigs, the behaviour of the catecholamines noradrenalin and adrenalin as well as the monoamine oxidase activity was biochemically studied following a local irradiation with 250 up to 6000 R surface dose. The noradrenalin content is significantly reduced already after a surface dose of 250 R. This drop of the noradrenalin content is beginning 15 min after irradiation, and not till 72 hours later, a complete normalization of the noradrenalin content is to be shown. A fractionated irradiation with twice 250 R SD in an interval of 24 hours leads to a further reduction. The changes of the adrenalin content are uncharacteristic, the activity of the monoamine oxidase is unaffected.

[Studies on the effect of radiation on electrolyte changes and metabolism of the myocardium. V. Changes in enzyme activities and glycolysis metabloites due to radiation]. / Untersuchungen über den Einfluss von Röntgenstrahlen auf Elektrolytver-schiebungen und Stoffwechsel des Herzmuskels

The behavior of enzyme activities, substrates and metabolites of glycosis as well as of the pentose phosphate shunt following local irradiation (250 to 6000 R surface dose) is biochemically investigated in the guinea-pig's myocardium. During irradiation, an activation of phosphorylase-a is going on while the total phosphorylase content remains unchanged. Enzyme activities of hexokinase and phosphofructokinase are increased in dependence on dosage as well as time. The glycogen content is being reduced; tissular concentration of the metabolites glucose-1-phosphate, glucose-6-phosphate, glyceraldehyde-3-phosphate, glycerol-3-phosphate, and pyruvate increases following irradiation; the content of fructose-1,6-diphosphate, dihydroxyacetonephosphate, and lactate is decreased. The activity of glucose-6-phosphate dehydrogenas is slightly inhibited, whereas 6-phosphogluconate-dehydrogenase remains unaffected.

[Sacrococcygeal chordoma in childhood]. / Das sakrokokzygeale Chordom im Kindesalter

A extremely rare case of sacrococcygeal chordoma in the infancy is communicated and it is discussed about the diagnose, therapy and clinic of these tumors with regard to the literature.