[Initial symptoms of hyperthyroidism in a young man with lumbar pain].
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Biomedical subjects
Publications and source records attributed to W Jellinghaus.
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Leiomyosarcomas of the spermatic cord are very rare tumours, which, in contrast to the rhabdomyosarcoms of childhood, occur almost exclusively in adults. We report the case of a 51-year-old male patient with a metastasizing, pleomorphic leiomyosarcoma of the spermatic cord. The tumour showed paraneoplastic secretion of beta-chain human chorionic gonadotropin (beta-hCG), as was demonstrated by the elevated levels of beta-hCG in serum samples and by immunohistochemistry. Histologically, the tumour was a high-grade leiomyosarcoma which showed an aggressive course with pulmonary metastases appearing 4 months after primary surgery. A concomitant rise in the serum levels of beta-hCG was also noted at this time. A wide spectrum of tumours with a choriocarcinomatous component or paraneoplastic production of beta-hCG has been described, the vast majority being carcinomas. Only two leiomyosarcomas producing beta-hCG have so far been reported. The paraneoplastic production of beta-hCG should prevent confusion with germ-cell tumours, especially teratomas.
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Visual examination, electron-microscopic observation and infrared-spectroscopic analysis demonstrate that the thermodynamically unstable calcium oxalate trihydrate, which supposedly plays an important role in the formation of certain urinary calculi, is a commonly occurring constituent of urinary stones.
Cell kinetic studies on the effect of vincristine (VCR) on cells in different cell-cycle phases were carried out using single- and double-labeling methods with 3H- and 14C-thymidine. Studies on mouse L 1210 and JB-1 ascites tumor cells, mouse jejunal crypt cells as well as on HeLa cells have shown that VCR affects cells not only during or prior to mitosis, but also cells that are in S phase at the time of VCR application. These cells are arrested during the next mitosis. Cells arrested in mitosis even with small doses of VCR subsequently become necrotic. Thus, it has been shown experimentally that an in vivo synchronization of tumor cells cannot be achieved with VCR and, therefore, the effect of a so-called synchronization therapy with VCR is not due to synchronization of tumor cells.
Over a ten year period, the authors have collected 120 cases of germinal tumours of the testis (35 seminomas and 85 non-seminomatous tumours). The largest single group was of mixed non-seminomatous tumours. The treatment of pure seminomas gave 100% good results by a combination of unilateral orchidectomy, radiotherapy and, in the case of stage III tumours with spread, chemotherapy. The prognosis of non-seminomatous tumours was dependent essentially upon the stage of spread. During the past three years, the best results of chemotherapy have been obtained with the combination of vincristin, bleomycin and platinum (1978, 1979, 1980). In his time, at stage I and stage II, all the patients are alive. Treatment consisted of a minimum of unilateral orchidectomy and retroperitoneal lymphadenectomy, Chemotherapy was envisaged only for those tumours with evidence of lymph node involvement. At stage III, they lost 3 patients out of 7, this being an excellent result bearing in mind the gravity of such tumours.
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Ftorafur (FT), a 2-tetrahydrofuryl derivative of 5-fluorouracil (5-FU) was introduced into cancer chemotherapy with the hope to obtain a therapeutic effect comparable to 5-FU with a smaller dose and less side effects. A comparison of the effect of FT and 5-FU on the proliferation of L 1210 ascites tumor cells in the present work has shown that both drugs result in an inhibition of DNA synthesis due to an inhibition of thymidylate synthetase. However, the extent of the effect of FT is reduced, i.e., to achieve a cell kinetic effect comparable to that of 5-FU, 60 times the equimolecular FT dose has to be applied. Thus, there is no dose-saving effect of FT compared to 5-FU. A depot-like 5-FU effect of FT due to a slow release of 5-FU from FT as described in the literature could not be confirmed in the present study either. The effect of FT on the proliferation of L 1210 ascites tumor cells did not last longer than that of 5-FU. In contrast to 5-FU a severe side effect, viz., a drastic decrease of the body temperature from 39.1 degrees to 31.6 degrees C, was observed. That means that FT cannot only be effective by a release of 5-FU. This toxic side effect must be due to a different mechanism of action of FT. A significant increase in the median life span could only be achieved by the application of 5-FU (180 microgram/g). An equimolecular FT-dose did not result in an increase of the median life span. Based on the present study, the advantages of FT compared to 5-FU described in the literature cannot be confirmed. The present work shows that cell kinetic studies in animals are a useful tool to test the effect of new drugs in chemotherapy.
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The cell line EB 33 was cultivated from the tissue of a human prostate adenocarcinoma in June 1973. Since that time, efforts have been made by scientists in several laboratories to characterize this line by morphologic, biochemical, endocrinologic, genetic, and immunologic parameters. The great need for a well-defined prostatic cell line for immunologic experimentation warrants a complete review of the subject.
The mechanism of action of the alkaloid vincristine (VCR) has been investigated in vitro on HeLa cells in culture and in vivo on jejunal crypt cells of the mouse. The in vitro experiments with HeLa cells show that VCR affects not only mitotic but also interphase cells. The VCR-affected cells first continue their passage through the cell cycle undisturbed but after reaching mitosis they are arrested in metaphase. This agrees well with the results obtained by Madoc-Jones & Mauro (1968) and Madoc-Jones (1973) on synchronized cell cultures. Until now there has been no investigation of the mechanism of action of VCR in vivo. This is due to the absence of a suitable technique for synchronization in vivo. The present study is based on a method which permits the assessment of the VCR sensitivity as a function of the cell age without synchronization in the usual sense. The jejunal crypt epithelium of the normal mouse was double labelled with 3H- and 14C-thymidine (TdR) in such a way as to produce a narrow subpopulation of crypt cells with a maximum age difference of 1 hr. On autoradiographs these cells can be distinguished by their characteristic labelling from other cells. As this 'pseudo'-synchronized subpopulation passes through the cycle the effect of VCR can be studied, i.e. one can analyse the effect in well-defined time intervals of the cycle. The results show that the effect of VCR is the same in vivo as in vitro. The crypt cells which are affected by VCR in interphase continue their passage through the cycle, but upon entering mitosis they are arrested in metaphase. VCR has, at the concentration used in the present study, no effect on the duration of the S and G2 phases. The necrotic cells seen after VCR application are formed from arrested metaphases.
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Tissues from human prostatic carcinomas and adenomas as well as cells from permanent cell lines originating from such tumors were transplanted into the subcutaneous space of "nude" mice. A total of 208 such transplantations were carried out. For transplantation of primary tumor tissue several techniques were used. Transplantation of single pieces of about 50 mg of tissue from carcinomas and adenomas provided the best results. With this technique carcinoma tissue was recovered from five of 10 tumors transplanted into 46 "nude" mice. Carcinoma was found in seven of 25 "nude" mice that were castrated and treated with testosterone but only once in 21 transplantations into castrates without testosterone substitution. This may suggest that heterotransplants of human prostatic carcinoma tissue can be established more easily in testosteronized animals. In the case of adenoma transplants, the histological picture was strikingly similar to the original tumors. Secretory activity was found in some acini, squamous metaplasia in others. Heterotransplantation of cells from permanent cell lines resulted in fast growing carcinomas without similarity to the origianl tumors. Dependence on hormones for growth of EB 33 and MA 160 cells in "nude" mice was not shown.
Chromosomal studies were performed on primary cultures from human prostatic adenomas and carcinomas. All cells from both tumor types showed diploid chromosomal counts with a normal human karyotype. Chromosomal analysis was also performed on cells of the permanent epithelial line EB 33 derived from a human prostatic carcinoma in this laboratory. In contrast to the primary cultures, hypotriploid chromosome numbers were found during continuous culture for more than 1 year. The range of chromosome numbers increased with time in culture and was reduced to the original model number of 64 by only one animal passage ("nude" mice). Feulgen fluorometry on different passages of the permanent cell line EB 33 showed tetraploidy. This discrepancy to the hypotriploid chromosome number can be explained by different Feulgen hydrolytic properties of the different cell types.
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Recent data show that carcinoma of the prostate is not radioresistant. But not all prostatic cancers are radiosensitive. All information available in the literature on histologically proven local destruction of prostatic cancer tissue, all survival data and reported complications after radiation treatment are reviewed and discussed. The results of radical surgical treatment from various authors but mainly from the series of Belt and Schröder are used for comparison. From these data it is evident that total prostatectomy of stage B and C tumors is superior to radiation therapy as far as local eradication of tumor goes. Five- and ten-year actuarial survival rates are about identical for stage B disease but favor total prostatectomy in stage C patients. Sexual impotence, the most important lasting complication of total prostatectomy, is present in 23-47% of patients after radiotherapy. Urinary incontinence is not known after irradiation but reported after surgery. Long term damage of the lower urinary tract, the gastrointestinal system, or the lymphatics was reported in 2-24% of patients after radiotherapy. The indication for radiation treatment in stage D patients is very questionable. Exact surgical staging by iliac and obturator lymphadenectomy is desirable to rule out stage D disease in locally confined tumors. Radiation treatment is indicated in patients who are not willing to undergo surgery, who are unwilling to accept sexual impotence, or who are poor candidates for surgery from other reasons.
Experiments are described on synchronizing L 1210 ascites tumor cells and jejunal crypt cells of the mouse with vincristine. In both cases the percentage of mitoses increases to a peak value 4 hrs after application of vincristine and decreases during the following 8 hrs ("releasing time") to the level of the normal mitotic index. Following this first mitotic peak no futher peak of neither the mitotic nor the labeling index was observed during 48 hrs in L 1210 ascites tumor cells and during 38 hrs in crypt epithelia. Thus, in both cell types it was not possible to obtain a synchronizing effect by applying vincristine. Based on cell kinetic considerations it was examined whether peaks of the mitotic as well as the labeling index can be expected at all under the given circumstances. The results show that the theoretical course of the mitotic index coincides with the measured values. This means that no peak of the mitotic index can be expected from the theoretical point of view. In calculating the time course of the labeling index the theoretical curve proved to depend to a high degree on the variations of the cycle time which are not known in detail, especially not after application of vincristine. However, the theoretical conditions show that also in the case of the labeling index no peak can be expected. This agrees with the experimental results. The general significance of a long "releasing time" of 8 hrs or more for the lack of a synchronizing effect is discussed.
The problem of whether vincristine can be used to synchronize partially cells in vivo was investigated. After injection of 0,0045 mug vincristine/g body-weight into mice practically all L1210-ascites tumour cells entering mitosis were arrested in metaphase up to the fourth hour. However, no second peak of the mitotic index was observed within 48 hours. Calculation of the theoretical mitotic index to be expected under the present experimental conditions also shows no second peak. The reason for this lack of synchrony is the long releasing time of the arrested cells.