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Biomedical subjects

R Ludwig

Publications and source records attributed to R Ludwig.

At least 91 records · Page 5Linked to original sources
PubMed1984

Chemical and biological stability of anticancer drugs used in a human tumor clonogenic assay.

Human tumor clonogenic assays (HTCA) are being used to evaluate the chemosensitivity of human cancers to both standard and experimental anticancer drugs as well as to predict clinical tumor response and resistance to these agents. To enable us to design and accurately interpret drug assay data we quantitated the chemical and biological stability characteristics of various cell cycle-specific and cell cycle-nonspecific drugs commonly used in our laboratory for chemosensitivity testing in the HTCA. Aliquots of the culture media were obtained immediately after drug addition and after 6 and 24 h and 2, 4, and 10 days of incubation, and then frozen in liquid nitrogen for later chemical (HPLC or RIA) and biological (HTCA) assay. Adriamycin, actinomycin D, bisantrene, bleomycin, and vinblastine retained 80-100% of their biological activity against human tumor colony-forming units even after 10 days of incubation in culture media. In contrast, etoposide lost 60% of its in vitro antitumor activity over the same period. There was no loss in the chemical concentration of actinomycin D. bisantrene, bleomycin, or vinblastine in the culture media, but etoposide concentrations as measured by HPLC decreased to zero over 10 days. We conclude that the HTCA can be used as a simple test for biological stability of new investigational agents prior to the development of adequate chemical assay methodology, and that it can help clarify whether a drug's in vitro antitumor activity is due to the parent compound or to a degradation product.

Antineoplastic Agents↗
PubMed1983

Functional characterization of T lymphocytes grown in semisolid agar.

T lymphocyte colony forming cells (TL-CFC) grown in agar in the presence of PHA were assayed for their capacity to induce or suppress polyclonal PWM dependent B lymphocyte differentiation into plasma cells. This was measured by identifying cells containing intracytoplasmatic immunoglobulins by direct immunofluorescence. To validate the helper and suppressor system used in this paper, the inductive capacity of unfractionated T lymphocytes and their subpopulations bearing Fc-receptors for IgM (TM) and for IgG (TG) was measured. The unfractionated T cells and the TM fraction showed helper activity, whereas the TG cells expressed suppressor activity. The TL-CFC grown in agar in the presence of PHA manifested helper activity at low cell concentration. However, increasing the TL-CFC concentration finally caused suppression of B cell differentiation. The suppressor effect could be abolished by prior irradiation of the TL-CFC before seeding them in agar. These results indicate that T cells grown in agar have the functional capacity of T helper and T suppressor cells to induce and suppress polyclonal PWM dependent B lymphocyte differentiation into plasma cells.

B-Lymphocytes↗
PubMed1982

The glia types inthe visual system of adult rats, their shape variability, distribution patterns, and their lightoptically visible contacts to other tissue structures.

In silver impregnated coronal sections of adult rat brains the glia types of the Corpus geniculatum laterale, pars dorsalis (CGLd) an in area 17 were registered considering their form variants (FV), their intraareal distribution and their light optically demonstrable connexions to other tissue structures. Compared with the shape-determining light optically visible processes and perikarya, astrocytes show the lowest, microglial cells the greatest from variability. Transitional forms between the three glia types were not detected, but between elongated astrocytes and fiber astrocytes. An accumulation of elongated astrocytes, fiber astrocytes, and oligodendrocytes was found in the lateral zone of the CGLd, of protoplasmic astrocytes in the lateral and intermediary zones and at the rostral and caudal poles of the griseum, too. In the cortex distribution differences in the single laminae became also evident. Astrocytes were most concentrated in L I, oligodendrocytes and microglia, however, in L V. A few FV of the microglia were found to show a predominant localisation in specific laminae. Neither the total glia number nor the single glia types correlate with the neuron packing density. The frequency distribution of the FV of oligodendroglia in the CGLd and the visual cortex is similar, that of microglia, however, significantly deviating. Compared with the CGLd the oligodendrocytes of area 17 have smaller somata. Astrocytes, oligodendrocytes and microglial cells reveal structural contacts to different parts of the neurons, to blood vessels and other glial cells, too. Contacts between oligodendrocytes and microglial cells as well as astrocytes in satellite position could never be observed. In the cortex a few FV of microglia show typical connexions.

Animals↗
PubMed1981

[Tumor stem cell cultures on agar: 1st results].

Hamburger and Salmon have recently developed an in vitro assay for human tumor stem cells which permits formation of colonies of human solid tumors and lymphomas in soft agar. In 50 patients with solid tumors or lymphomas studied by us, tumor colonies grew from effusions and biopsies in 75% of patients (17 of 21) with histologically or cytologically involved specimens. Lymphoid colony growth was obtained in about 25% of specimens (5 of 19) including malignant lymphomas. Conversely, no colony growth was observed in 10 cases where the biopsies or effusions were histologically or cytologically negative. The effect of various conditioned media on tumor growth in agar was investigated. Colony formation of solid tumors was promoted to an especially marked extent by cell-free malignant effusions. This assay yields satisfactory results in solid tumors and appears useful for investigation of different cytotoxic effects of anticancer drugs on the survival of human tumor colony-forming cells.

Agar↗
PubMed1981

Combined erythrocyte glucosephosphate isomerase (GPI) and glucose-6-phosphate dehydrogenase (G6PD) deficiency in an Italian family.

A severe hemolytic crisis was observed in a 5-year-old boy of Italian origin. Analysis of his hemolysate revealed a hemizygous deficiency of glucose-6-phosphate dehydrogenase (G6PD) and a heterozygous deficiency of glucosephosphate isomerase (GPI). According to the literature this is the fourth family with a combined deficiency of these two enzymes located on different chromosomes. Only the G6PD deficiency seems to be responsible for the hemolytic crisis.

Anemia, Hemolytic↗
PubMed1981

[Bone metastases in Wilms' tumor in relation to histologic grading (author's transl)].

86 patients with Wilms' tumor were treated in Heidelberg between 1951 and 1980. Using the histopathologic grading according to Hardwick and Stowens the sarcomatous tumor type has an unfavorable prognosis. All the patients in stage III to V developed metastases. In contrast to other types of Wilms' tumor these sarcomatous tumors do metastasize to bones, not primarily to the lung. Boys up to 5 years are mostly affected by the tumor. These were "cold" lesions in bone scan using different radionuclides on skeletal osteolytic metastases, which is limiting the application of scans to detect bone metastases in Wilms' tumor. A more aggressive chemotherapy should be given to improve prognosis of the sarcomatous type of Wilms' tumor.

Bone Neoplasms↗
PubMed1981

Thymic involvement and initial white blood count in childhood acute lymphoblastic leukemia.

From 1970 to 1977, two nonrandomized groups of children with acute lymphoblastic leukemia (ALL) were treated with two different induction regimens. A total of 168 patients (group DAL) received induction therapy closely adapted to St. Jude protocol VII. A total of 119 patients (group BFM) were treated with the West Berlin induction protocol. Evaluable for analysis were 138 patients of group DAL and 113 patients of group BFM. Thirty children had thymic involvement (Thy+), 15 in each group. In children without thymic involvement (Thy+), the median initial white blood count (WBC) was 8400/mm3 in group DAL and 8000/mm3 in group BFM. In contrast, the initial WBC was 42,000/mm3 and 79,200/mm3 in the corresponding group with thymic involvement (Thy+). The probability of continuous complete remission (CCR) at 9 years is 0.41 +/- 0.05 for patients without thymic involvement and 0.09 +/- 0.09 for patients with thymic involvement in group DAL, and 0.65 +/- 0.05 for those without thymic involvement and 0.52 +/- 0.13 for those who had thymic involvement in group BFM. After adjustment for initial WBC (regression analysis) the presence of thymic involvement was still a predictor of poor outcome in group DAL (p less than 0.001), whereas it was not a predictor of poor response in group BFM. In view of comparable patient composition in both treatment groups, the favorable prognosis in BFM patients has to be related to the mode of induction therapy.

Adolescent↗
PubMed1980

[Autoantibodies in malignant tumors].

Autoimmune phenomena are to be referred to the possible immune reactions of the host organism in malignant tumours. By means of the indirect immune fluorescence method in 95 sera of patients with tumours and a control group 0f 30 blood donors was sought for autoantibodies against mitochondria, nuclear factors, smooth musculature, myocardium, delomorphous cells. In the blood donors in one case autoantibodies against the myocardium could be proved, the tumor group, however, revealed positive findings of autoantibodies in 25 patients, which are statistically significant (p < 0.05). In the individual groups of diagnosis the acute myeloic leukaemia, the IgG-plasmocytoma and the cervical carcinoma showed a highly significant positive proof reaction compared with the control. The titres lie in their highest values at 1 : 64, in most cases at 1 : 16 and 1 : 32 and speak for an accompanying reaction are epiphenomenon. Autoantibodies against mitochondria were in no case found against smooth musculature in all positive groups. Apart from the absence of antibodies against delomorphous cells in gynaecological tumours the differentiation of types of autoantibodies do not show a reference to kind of tumour and localisation. The proof of autoantibodies in malignant tumours should be used for the judgment of the immune state

Antibodies, Neoplasm↗
PubMed1980

[Therapy-related central nervous system complications in acute lymphoblastic leukemia and non-Hodgkin's lymphoma of childhood (author's transl)].

An increasing number of children with acute leukemia show cerebral complications. 10 out of 78 children treated in our hospital for acute lymphoblastic leukemia or non-Hodgkin's lymphoma who underwent remission induction therapy or were in continuous complete remission developed central nervous system complications. During intensive initial therapy, intracerebral hemorrhages (2) and metabolic disturbances with concomitant cerebral convulsions (3) were seen. Unusual central-nervous infections occured in each treatment period (3). Cerebral degenerations could be observed only during the maintenance therapy (2). Cerebral convulsions were the leading symptom in 7 children. With intensive control of the coagulation system and the metabolic parameters central nervous system complications in the treatment of acute lymphoblastic leukemia should be reduced significantly.

Adolescent↗
PubMed1980

Breast involvement in non-African Burkitt's lymphoma.

A patient with non-African Burkitt's lymphoma is reported in whom bilateral breast involvement was detected by both mammography and 67-Ga-citrate scintigraphy. The causes of breast uptake of 67Ga-citrate are reviewed, and it is noted that not only asymmetrical increases in uptake of 6767Ga-citrate are indicative of disease.

Adult↗
PubMed1979

[ZNS complications in children with acute lymphatic leukemia. Computer tomographic studies].

78 children with acute lymphoblastic leukemia or non-Hodgkin-lymphoma were treated at the Children's Hospital of the University of Heidelberg from December 1971 to April 1979. Following cytostatic treatment and irradiation of the skull 11 children developed CNS-symptoms (mainly seizures and paresis) which were caused by intracerebral hemorrhage, infectious or degenerative CNS-diseases. Cranial axial tomography (CAT) was helpful in finding the cause of the CNS-complication. We recommend routine CAT in the beginning and during the course of treatment of leukemia to document CNS-changes as early as possible and to prevent further damage by alterations of therapy.

Adolescent↗
PubMed1979

Assessment of adriamycin cardiotoxicity in children by systolic time intervals.

In a prospective study, 44 children receiving Adriamycin (ADR) for various neoplastic diseases underwent serial estimations of the systolic time intervals (STI) for the noninvasive assessment of left ventricular myocardial performance. Five of the 44 children developed clinical signs of ADR-related congestive heart failure at a cumulative dose of less than 550 mg/m2 body surface area. Clinical symptoms, changes in the electrocardiogram and in the chest X-ray were preceded in every case by changes of the STI, mainly a prolongation of the left ventricular pre-ejection period (PEP), or a decrease of the ejection time (ET)/pre-ejection period (PEP) ratio (ET/PEP). A continous increase of the PEP and a decrease of the ET/PEP-ratio also gave an indication of myocardial dysfunction during ADR treatment in the other children without clinical signs of congestive heart failure. This subclinical cardiotoxic effect of ADR below the critical cumulative dose of 550 mg/m2 was observed in children with pre-existent myocardial damage, with preceding thoracic irradiation, or during concurrent chemotherapy, of which cyclophosphamide seemed to be most important. Thus, the estimation of the STI proved helpful and reliable in the early detection of incipient heart failure and in the selection of high risk patients in children receiving ADR treatment.

Child↗