[Operating in the home. Ambulatory care by a visiting nurse from a pediatric cancer ward].
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Caregivers↗
Biomedical subjects
R Ludwig
Publications and source records attributed to R Ludwig.
Augmented MYCN expression advances the malignant phenotype of human neuroblastoma cells: evidence for induction of autocrine growth factor activity.
Amplification and enhanced expression of the MYCN oncogene are thought to contribute to the development and progression of human neuroblastomas. Here, we have transfected human neuroblastoma cells that harbor a single MYCN gene copy with the human MYCN gene driven by a viral enhancer/promoter, and we have compared the properties of the parental and the transfected cells. The transfected cells show an enhanced expression of the exogenous MYCN gene. Unlike the parental cells, they have acquired an increased proliferative potential, induce tumors in nude mice, grow in soft agar, and require low amounts of exogenous growth factors in order to proliferate. The MYCN-transfected, but not the parental, cells can synthesize and utilize autocrine growth factor activity. These results demonstrate that enhanced MYCN expression contributes to malignant progression of human neuroblastoma cells, conceivably by stimulating the expression of autocrine growth factor activity.
Animals↗
[The importance of preoperative chemotherapy and radiotherapy in 373 children with Wilms' tumor].
Between 1980 and 1988, in a prospective study of 373 children with Wilms' tumour throughout the Federal Republic of Germany, the results of various pre- and postoperative treatment schedules were analysed. There were 184 boys and 189 girls, mean age 3 11/12 (0-27) years. One third each was in group I, II or III-V, respectively. In 52% of cases the tumour volume, measured by ultrasound, was more than 400 ml. 218 of the children were called protocol patients, the remaining 155 served as observation patients, because the latter had histological variants or there had been marked treatment deviations. The stage-adapted treatment always included operation, in 30% of children after pre-operative chemo- or radiotherapy. Radiotherapy was given in selected patients in stage II and always to those in stages III, IV or V. Chemotherapy consisted of Actinomycin D and vincristine, adriamycin was added for stages III-V and cyclophosphamide or ifosfamide for histologically highly malignant variants. Of the 218 protocol patients 196 (90%) were alive without recurrence, after a mean observation time of more than 7 years. Radiotherapy was given to only 105 of the 218 protocol patients. The prognosis of the 155 observation patients differed according to the histology: those with clear-cell type had a better prognosis than previously reported. Among the total group of 373 patients 305 (81.8%) have remained without recurrence after more than 6 years.
Adolescent↗
[Life style and quality of life of children and adolescents following malignant tumor disease].
Psychosocial support after the diagnosis of childhood cancer is absolutely necessary to help not only the patients but also the parents, family members, and friends to deal effectively with the emotion and social problems arising from the disease. Psychological support for the whole family, rooming-in facilities on the ward, parent-self-help-groups, social and financial helps reduce problems which flow from such a diagnosis and may develop a positive coping strategy. Experiences over a long period of psychosocial aftercare in the University Hospital of Heidelberg are analyzed and some scientific data of this model are reported.
Adaptation, Psychological↗
[A total subcutaneously implantable venous catheter system. 4 years' experience in cancer patients].
A totally implantable venous access system (Port-a-Cath) was inserted in 48 cancer patients. The devices were utilized for the administration of chemotherapy, antibiotics and blood products, as well as for blood drawing. Implantation was possible on an outpatient basis. The system provided full physical activity and good quality of life for the patient. Complications related to the Port-a-Cath were one subclavian vein thrombosis, one catheter thrombosis, two catheter dislocations, one dislocation of the "port" and reduced blood aspiration in two cases. It is stressed that no catheter related infections were seen. With increasing experience of the team the complication rate was significantly reduced.
Anti-Bacterial Agents↗
[Chemotherapy of soft tissue tumors].
The use of chemotherapy in the treatment of patients with advanced soft tissue sarcoma and as adjuvant and neoadjuvant therapy is reviewed. In advanced disease a response rate of up to 35% can be achieved with combination chemotherapy, but these are mainly partial remissions; few complete remissions are attained. The median survival for patients in partial remission is 2 years. The most active cytotoxic drug is adriamycin, with a remission rate of 30%. The addition of dacarbazine can increase the remission rate; however, this has no significant impact on survival and the toxicity is more pronounced. The activity of neoadjuvant or adjuvant chemotherapy is still controversial. Some studies indicate a positive effect on disease-free or overall survival with adriamycin-containing regimens. Other studies have not confirmed these results. More controlled trials with adequate numbers of patients stratified for tumor subtype, tumor localization and grading are needed to define the value of adjuvant or neoadjuvant chemotherapy in soft tissue sarcomas. Optimal interdisciplinary treatment can only be realized at specialized centers.
Antineoplastic Combined Chemotherapy Protocols↗
[Changes in the blood-cerebrospinal fluid barrier for serum proteins in children with acute lymphatic leukemia].
The blood-CSF barrier inhibits permeation of most chemotherapeutic agents into the central nervous system (CNS). The influence of systemic chemotherapy and prohylactic CNS irradiation on the permeability of the blood-CSF barrier was studied in 49 children treated for acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma. To study the permeability of the blood-CSF barrier under treatment according to BFM-ALL protocols, nephelometric determinations of albumin, immunoglobulin G (IgG), and alpha-2-macroglobulin in serum and CSF and total protein in CSF were performed at several time intervals during chemotherapy and prophylactic cranial irradiation. During systemic induction chemotherapy, no significant changes of blood-CSF barrier could be observed. In contrast, in the course of prophylactic CNS irradiation and intrathecal methotrexate application, a significant elevation of albumin, alpha-2-macroglobulin and total protein in CSF, and a significant decrease of blood:CSF ratios for albumin and alpha-2-macroglobulin were observed. IgG did not change significantly. After prophylactic CNS treatment and during maintenance chemotherapy protein concentrations and blood:CSF ratios gradually returned to normal range. This normalization was accelerated by cortisone treatment during the reinduction period.
Adolescent↗
Dihydrofolate reductase-activity in brain tissue. Effect of X-irradiation.
The mechanism responsible for the toxic late effects of cranial irradiation, followed by the administration of systemic methotrexate (MTX) on brain tissue, is still under discussion. We studied the influence of X-irradiation on dihydrofolate reductase (E.C. 1.5.1.3) activity (DHFR), the enzyme inhibited by MTX. New Zealand white rabbits, 6-9 weeks old, underwent 24 Gy fractionated or 20 Gy single-dose brain irradiation using a 60Co source. Before, immediately following, and 1, 2, 4, 12 weeks after irradiation, DHFR was measured in brain and liver tissue by a photometric assay. DHFR in brain tissue was 11.9 +/- 2.9 mU/g wet weight (ww) X h and in liver tissue 121.8 +/- 24.2 mU/g ww X h. Fractionated brain irradiation with 2 Gy per day produced no significant changes in brain DHFR. Single-dose cranial irradiation significantly decreased brain DFHR (7.3 +/- 0.6 mU/g ww X h). Suppression of the developmental increase of DHFR by X-irradiation in young rabbits could be excluded by determining the unchanged brain-to-liver ratios of DHFR in the animals with fractionated brain irradiation.
Animals↗
Effects of local irradiation and i.v. methotrexate on brain morphology in rabbits: early changes.
Brain damage following cranial radiation therapy can be crippling or even life-threatening and has been studied in both patients and animals. An additional toxic effect of chemotherapy has been found in children, who died following brain irradiation and systemic chemotherapy for the treatment of acute lymphoblastic leukemia. To study the interaction of radiation and drugs on brain tissue, we treated rabbits with brain irradiation and/or i.v. methotrexate. For a period of up to 3 months following radiation therapy, brain morphology was compared in seven treatment groups. Weekly doses of methotrexate administered i.v. produced no brain damage. Histological examination showed myelin swelling and beading 14 weeks after fractionated brain irradiation with 24 Gy. Combination of brain irradiation and methotrexate produced additional hypertrophy of microglia and pyknosis of adventitial cells. In none of these groups, even after doses of 48 Gy brain irradiation, was calcification or brain necrosis observed during the first 14 weeks following irradiation.
Animals↗
Clitoromegaly and abdominal tumour as leading signs of a mediastinal non-Hodgkin lymphoma.
A 2-year-old girl was admitted with clitoromegaly, mediastinal tumour and enlarged kidneys. A seventh cranial nerve palsy was associated with an increased cell count in cerebrospinal fluid. The diagnosis of a lymphoblastic lymphoma was confirmed by a cervical lymph-node biopsy. Six years after diagnosis and treatment according to the BFM protocol the girl remains in first complete remission.
Abdominal Neoplasms↗
Making boxing safer. The Swedish model.
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Adolescent↗
Effects of methotrexate on rabbit testes. Part 1: Morphological changes.
Methotrexate (MTX) has the potential of eradicating small infiltrations of leukemic cells in the gonads. We examined the morphological changes in rabbit testes after a single dose (57.5 mg/kgBW) or repeated low doses (6 mg/kgBW once a week for 14 weeks) of MTX IV. Fertility rate and spermatogenic activity were evaluated using the tubular fertility index (TFI). Testicular MTX concentrations (measured by RIA) were in the same range in both groups. Only after repeated MTX application were reduction of TFI and signs of germinal cell line degeneration found. When given repetitively, MTX therapy may modify the fertility and tubular morphology. Long-term follow-up will show how these changes affect future fertility.
Animals↗
Effects of methotrexate on rabbit testes. Part 2: Hormonal changes.
Thirty mature and peripubertal male rabbits were examined for endocrine function and tissue methotrexate (MTX) concentration after single (57.5 mg/kgBW, group 1) and repeated (6 mg/kgBW, once a week for 14 weeks, group 2) MTX doses. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and androstenedione plasma levels were measured by radioimmunoassay (RIA). We found elevated plasma FSH levels in both groups. Elevated plasma androstenedione level and reduced plasma testosterone level in group 2 suggest an enzymatic defect in the gonadal steroid synthesis. Unchanged LH plasma level, when compared to controls, is thought to be the result of a combined effect of MTX on the gonadal steroids and gonadotropin synthesis.
Androstenedione↗
[Brain metastases as primary manifestation of non-small cell bronchogenic carcinomas].
While brain metastases from small cell lung cancer are a familiar problem, the incidence of brain metastases from non-small cell lung cancer, and their significance as the first tumor manifestation, has been underestimated. At the University Hospital, Basle, over one year, 7 (approximately 7%) of 102 patients with newly diagnosed non-small cell lung cancer had brain metastases as the first manifestation of systemic cancer. Three of the 7 patients were women with a mean age of 48 years. Initial symptoms were headaches, vertigo and vomiting, which prompted the diagnosis of brain metastases. In only 3 patients was the primary lung cancer diagnosed immediately after diagnosis of the brain metastases, while in the remaining 4 a period of up to 6 months elapsed. Bronchogenic cancer is the most frequent primary in patients presenting with brain metastases. Accordingly, in a patient with brain metastases from an unknown primary, bronchogenic cancer should be considered first and diagnostic tests aimed in that direction. This may obviate an extended and expensive diagnostic workup.
Adult↗
Pharmacologic pitfalls in the human tumor clonogenic assay.
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Animals↗
Evaluation of schedule dependency of anticancer drugs in the human tumor clonogenic assay.
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Antineoplastic Agents↗
Neurons of the superficial tectal gray. An intracellular HRP-study on the kitten superior colliculus in vitro.
An en bloc preparation of the mammalian superior colliculus in vitro has been used to study neurons of the superficial gray layer (SGS) with intracellular recording and HRP-technics. Electrophysiological data from kittens at 4-19 days of age suggest that at this stage SGS-neurons possess multiple spike trigger zones which can be activated by synaptic depolarization and are probably located on dendrites. In response to intratectal stimulation SGS-neurons generate EPSP-IPSP sequences or IPSPs. IPSPs are found in all penetrated cells as early as the 4th postnatal day. Ascending projection cells (APCs) and inter-layer cells (ILCs) have been identified based on antidromic activation and/or intracellular labeling with HRP. The extended dendritic arbor of APCs and ILNs (dorsal spread up to 10-20 microns below surface, horizontal spread up to 1100-1500 microns) enables these cells to sample visual information from a wide area of the visual field. Recurrent collaterals, in conjunction with potent inhibitory mechanisms, could contribute to the formation of receptive field properties of superficial tectal neurons. ILCs establish collateral connections with the intermediate gray layer.
Animals↗
Evaluation of anticancer drug schedule dependency using an in vitro human tumor clonogenic assay.
A human tumor clonogenic assay (HTCA) has been used to evaluate standard and experimental anticancer drugs with respect to their inhibition of clonogenicity of both fresh human cancers and human tumor cell lines. By comparing the inhibitory effect on tumor colony-forming unit (TCFU) growth of 1-h and continuous drug exposures in the HTCA we were able to identify and separate schedule-dependent (e.g., bleomycin, vinblastine, and etoposide) and schedule-independent drugs (e.g., actinomycin D, adriamycin, bisantrene, and cis-platinum). Vinblastine, bleomycin, and etoposide, which are known to have 'cell cycle-specific' characteristics, caused exponential reduction in tumor colony formation when given by continuous exposure, whereas when given with a short exposure each of these drugs caused plateau-type dose-response curves. For comparison of the relative efficacy of the two dosing schedules, a ratio (1-h versus continuous exposures) was calculated of the drug concentrations which reduced growth of TCFU to 50% of the control values (ID50) for fresh human tumors and human tumor cell lines. For fresh tumors, ID50 ratios for adriamycin, actinomycin D, and bisantrene ranged between 2 and 60 (median 14), whereas the ID50 ratios for bleomycin, vinblastine, and etoposide ranged between 100 and 3,000 (median 600). The fact that actinomycin D, adriamycin, and bisantrene (a new anthracene-type drug) had similarly shaped dose-response curves and very low ID50 ratios suggests that the cytotoxicity of these compounds may not be schedule-dependent. On the other hand, the steep dose-survival curves we observed after continuous drug exposure and the high ID50 ratios of bleomycin, vinblastine, and etoposide suggest that these drugs may possess schedule-dependent cytotoxicity characteristics. Before final conclusions are drawn concerning a drug's schedule dependency it is essential to evaluate its in vitro stability and protein-binding characteristics. Finally, it must be emphasized that unlike the results obtained with 1-h exposure studies, the in vitro continuous exposure schedules have yet to be shown to be predictive of clinical response for any agent or tumor type.
Antineoplastic Agents↗