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Biomedical subjects

U Willnow

Publications and source records attributed to U Willnow.

At least 19 recordsLinked to original sources

Total body hyperthermia in combination with etoposide and melphalan in a child with acute myelomonocytic leukemia.

In vitro and clinical studies have shown antineoplastic effects of hyperthermia alone and in combination with other treatment modalities. Synergistic cytotoxic effects of chemotherapy and hyperthermia have been demonstrated on leukemic cell clones in vitro. It seems that hyperthermia is effective in overcoming chemotherapy resistance. Several groups treated solid tumors by using total body hyperthermia (TBHT). However, only a few studies have been reported investigating the clinical effects of TBHT in myeloproliferative disorders. We report the case of a 7-year-old boy with myelomonocytic leukemia treated with TBHT (2 hours, 42 degrees C) combined with etoposide (600 mg/m2), melphalan (30 mg/m2) and hyperglycemia (200-300 mg/dl). Within 24 hours after TBHT, the leukemic cells decreased after TBHT from 53,000/microliters to zero. Skin leukemic infiltrates, resistant to conventional treatment, also responded well. Although our patient relapsed 34 days after TBHT, these results indicate that TBHT in combination with cytotoxic treatment may be a useful treatment modality in refractory leukemia.

Antineoplastic Combined Chemotherapy Protocols

Pre-emptive analgesia: comparison of preoperative with postoperative caudal block on postoperative pain in children.

We have compared in 25 children the effect of preoperative with postoperative caudal block on pain after circumcision in a double-blind, randomized study. After induction of anaesthesia, patients were allocated randomly to receive a caudal block either before (n = 14) or immediately after (n = 11) surgery. Postoperative pain was rated on a paediatric pain scale. If pain occurred, children received paracetamol in a dose related to body weight. Using the Mann-Whitney U test (significance < or = 0.05) there was no significant difference in cumulative postoperative analgesic requirements within the first 48 h and in times to first analgesic administration between the groups. Cumulative pain score, assessed every 30 min for the first 8 h after operation, was significantly lower for those patients who received caudal anaesthesia after operation. Thus we could not demonstrate any advantage in performing caudal block before compared with after surgery.

Acetaminophen

[Effect by proliferation kinetics of malignant tumors of children of hyperthermia].

Embryonal tumors (21 Wilms' tumors, 11 neuroblastomas, 9 rhabdomyosarcomas) and 16 sarcomas of the skeleton of childhood were studied with an autoradiographic in vitro method according to the responsibility to hyperthermia 42.5 degrees C/120 min, to Cyclophosphamide, to Doxorubicin, and to Actinomycin D, and also to the combined application of hyperthermia and cytostatic drugs. Hyperthermia alone reduced the median 3H-thymidine, respect. 3H-uridine incorporation between 38.1 and 56.8%, respect, 45.9 and 63.9%. Hyperthermia inhibited the RNA synthesis stronger than the DNA synthesis. The combined application of hyperthermia and the different cytostatic agents increased the inhibition of incorporation of the labeled precursors extraordinarily (by Cyclophosphamide to 81.6-90.8%, by Doxorubicin to 60.8-80.0, by Actinomycin D to 79.4-93.2%). In case of the inhibition of 3H-thymidine or 3H-uridine incorporation lower than 40% (resistance), in each case the combination of hyperthermia and cytostatic drug overcomes the resistance. The consequences of hyperthermia sensitivity testing of solid tumors of human beings are discussed.

Autoradiography

[Treatment of otherwise incurable tumor diseases in childhood using whole-body hyperthermia and chemotherapy].

Conventional methods of treatment having failed in 17 children (aged 9/12 to 16 5/12 years) with incurable solid malignant tumours underwent whole-body hyperthermia (41.8-42.0 degrees C, for 2-3 h), hyperglycaemia (20-25 mmol/l) and polychemotherapy. Five children had neuroblastoma (stage 4), three Wilm's tumour (stage 4 or 5, unfavourable histology), five skeletal sarcoma with metastases, three inoperable malignant liver tumour, and one brainstem tumour of unknown histology. Whole-body hyperthermia was induced by extracorporeal blood warming in an haemodialysis apparatus under neuroleptic analgesia, thermistors measuring the temperature in the oesophagus, rectum, trachea and skin. There were on average four treatment sessions (between one and ten, total 58), a week apart. The result could be assessed in 12 children: one persisting complete remission (19 months-metastasising renal rhabdoid tumour), eight partial or incomplete remissions, and three nonresponders (osteogenic sarcoma; Ewing sarcoma; brainstem tumour). If the risk can be satisfactorily judged the method is useful and of bearable toxicity. The results point to a high antitumour effectiveness of combined hyperthermia and chemotherapy.

Adolescent

[Malignant fibrous histiocytoma of the mandible in a 1 6/12-year-old boy].

A report on malignant fibrous histiocytoma of the mandible in a 1 6/12-year-old boy, a condition rarely seen in children. Because of inoperability radiotherapy was used resulting in complete tumour remission. The clinical course was complicated by a tracheo-oesophageal fistula and aspiration pneumonia. The spontaneous closure of the fistula occurred 5 months after tracheostomy and catheter jejunostomy. After 2 10/12 years there is no evidence of tumour disease. Possibilities and problems of therapy are discussed.

Child

[Simultaneous occurrence of Wilm's tumor and multiple lung hamartomas in a 15-year-old girl].

The observation of multiple adenofibroleiomyomatous hamartomas of the lung in a 15-year-old girl 7 years after treatment of a Wilms' tumour caused diagnostic difficulties that are discussed. The diagnosis was finally established by thoracotomy and tumour resection. The simultaneous occurrence of Wilms' tumours and benign or malignant tumours points to genetic factors in the development of both tumours.

Adolescent

[Therapy of testicular tumors in childhood].

Between 1954 and 1984 41 primary testicular tumours were treated in 40 children at the age of 0 to 9 years as well as 9 secondary testicular tumours in malignant systemic diseases or metastases. The histological reclassification of the number of cases revealed 15 yolk-sac-tumours, 10 differentiated teratomas of immature subtype, 1 intermediary malignant teratoma, 3 undifferentiated malignant teratomas, 2 Sertoli-cell-tumours (1 double-sided) and 5 rhabdomyosarcomas. 2 children each with undifferentiated malignant teratomas and rhabdomyosarcomas died, all before 1970. 5 children with yolk-sac-tumours and 2 with rhabdomyosarcomas who since 1974 have been treated with Ablatio testis and combination chemotherapy live without tumour. Histological classification and division into stages are proved and form the basis of a therapy conception which in all testicular tumours apart from the Ablatio testis contains the chemotherapy of different intensity (HTK-84), taking into consideration form of tumour, stage and age of the children. The retroperitoneal lymphadenectomy is recommended only in the proof of metastases.

Adolescent

The sensitivity testing of Wilms' tumors to cytostatic agents with an autoradiographic in vitro short-term test.

Sensitivity of 15 Wilm's tumors in children was tested towards cytostatic agents in vitro by means of an autoradiographic short-term test. Sensitivity was measured as a magnitude of the inhibition of 3H-thymidine, resp. 3H-uridine incorporation. The test was performed with Adriamycin, Actinomycin D. Daunomycin, Bleomycin, Cyclophosphamide, Ifosfamide, Trenimon, and Arabinosylcytosine. None of the tumors is resistant to all substances, they are responsive against 2 or more drugs. The most effective drugs tested are Adriamycin, Actinomycin D and Cyclophosphamide. The tumors show a marked individual sensitivity pattern. This behavior is explained mainly by the usually high proliferative activity of Wilms' tumors. The possibilities and limits of long-term and short-term methods for sensitivity testing are discussed critically. For the evaluation of the results of in vitro testing and in vivo effectiveness the close correlation should be considered between the type of cytostatic agent and proliferation kinetics of the tumor, cytostatic agent and effect on tumor metabolism as well as the effect of the cytostatics and the nucleic acid precursors used for the short-term test. Despite the methodological limitations preclinical testing should be preferred to unselected chemotherapy.

Antineoplastic Agents

[Cell proliferation kinetics of solid tumors in childhood].

With the aim to develop an improved individual therapy of tumor-affected children, tumor particles were in vitro incubated with radioactively labeled precursors in order to determine the parameters of cell proliferation kinetics. The growth rate of the tumors was derived from the 3H-uridine labelling index. A "cell kinetic therapy index" is calculated from the temporal ratio of the cell cycle phases S, G2, and M, which are sensitive to cytostatic compounds and radiation, and of the mean duration of the cell cycle. When the cell kinetic therapy index (ZTI) is below 0.2 chemotherapy is scarcely promising whereas it is promising at 0.5 and above. The experimental data of Wilms tumors, osteogenic sarcomas and rapidly growing neuroblastomas are in good agreement with the clinical rate of tumor remission.

Bone Neoplasms

Autoradiographic in vitro study of the cell kinetics of osteogenic sarcomas and Ewing's sarcomas in children.

Proliferation kinetic parameters of 9 osteogenic sarcomas (6 primary tumours, 3 lung metastases) and 3 Ewing's sarcomas were determined using an autoradiographic in vitro method (single and double labelling with 3H- and 14C-thymidine, and 3H-uridine). Osteogenic sarcomas and Ewing's sarcomas, respectively, showed clearly individual pattern of proliferation. The following values were obtained: The average 3H-thymidine labelling indices of 13.8/8.7%, the DNA synthesis times of 12.2/14.4 hours, mitosis times of 1.1/1.9 hours, and mean cell cycle times of 58.0/78.2 hours. The potential tumour doubling times determined with the inclusion of the growth fraction averaged 4.8/5.0 days. Using 3H-uridine labelling of tumours, autoradiography allowed the determination of the growth fraction fair accuracy. It is between 0.26 and 0.71 for osteogenic sarcomas, the average being 0.49. In vitro results were compared with the volume doubling times of metastases of osteogenic and Ewing's sarcomas, reported in the literature which had been determined from series of lung radiographs. The importance of cell kinetic studies of human tumours therapy is demonstrated by a "cell kinetic therapy index".

Autoradiography

[The role of cell proliferation kinetics and cytostatica - test for sensitivity of neuroblastomas, recurrent tumours and tumour metastases (author's transl)].

Using auto-radiographic techniques in vitro studies performed to analyse the growth rate in 13 cases of neuroblastoma, 6 recurrent tumours (assorted) and 7 metastatic tumours. The cell kinetic parameters using 3H thymidine markers, DNS synthesis, mitotic rate and mean cycle rate were investigated. The growth rate can only be calculated approximately. The results show that neuroblastomas grow incredibly fast. The cell-cycle period varies between 13.1 and 266.3 hours and averages 71 hours. Recurrent tumours have a tendency to have the same growth rate as the primary tumour. Primary metastases of Wilm's tumours and osteogenic sarcomas proliferate rapidly with a cell-cycle of 13.0- 87.0 hours (average 37.7 hours). All tumours have a distinctly individual proliferation pattern. Cell division and growth rate of malignant tumours are important in relation to radiotherapy and the use of cytotoxic drugs. These factors are expressed as a "cell-kinetic therapeutic index", which helps to predict the effectiveness of cytotoxic drugs and radiotherapy. Two cases of neuroblastoma were classified as resistant. Most tumours excluding the fibrosarcomas react well against two cytotoxic reagents. The cell-kinetic pattern and the sensitivity results are used in determining the treatment of recurrences and metastases. The relationship of these investigations in clinical practice is discussed.

Antineoplastic Agents

[Mesoblastic nephroma--a malignant tumor with low grade of malignancy].

The mesodermally differentiated and only in newborns and young infants occurring mesoblastic nephroma is regarded as benign. Recidivations with malignant course, inclination to infiltration and richness in mitosis make arise doubts about the benignity despite good prognosis. The results of a proliferation-kinetic examination received by an autoradiographic in vitro method of a mesoblastic nephroma which was observed in a 20-day-old infant are characteristic for a malignant tumour of low degree of malignity: 3H-thymidine marking index 5.8%, DNA synthesis time 18.2 hours, mean generation time 141.1 hours (= 5.9 days). Growth fraction 0.28 and potential doubling time of the tumour 16.4 days. These data decisively deviate from those of the Wilms-tumours, which are cell-kinetically characterized as extraordinarily quickly growing, highly malignant tumours. The position of the mesoblastic nephroma in the system of the dysontogenetic renal tumours is briefly discussed. The ureteronephrectomy performed in time is the only necessary therapeutic measure, since also the mesoblastic nephroma follows the general rule of dysontogenetic tumours that the prognosis is the better the younger the infant is.

Humans