Search PubMed⌕ Search

Biomedical subjects

C U Ludwig

Publications and source records attributed to C U Ludwig.

30 records · Page 2Linked to original sources

[Infusion pumps and subcutaneously implantable catheter systems as an aid in the ambulatory care of tumor patients].

Totally implantable catheters have greatly improved therapy and supportive care of tumor patients. Venous catheters can reduce the problem of maintaining reliable vascular access and the risk of cytotoxic drug extravasation. In addition, epidural or intrathecal catheter systems can result in an improved pain relief and in reduced side effect incidences in many patients suffering from severe cancer pain. The intraarterial and intraperitoneal catheters facilitate loco-regional chemotherapy. If used by an experienced team, most of these systems have a relatively low complication rate. The combination of such catheters with portable pumps does further facilitate the management of ambulatory tumor patients and will improve their quality of life.

Ambulatory Care↗

[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↗

Prevention of cytotoxic drug induced skin ulcers with dimethyl sulfoxide (DMSO) and alpha-tocopherole.

Accidental subcutaneous extravasation of several antineoplastic agents may provoke skin ulcerations for which there has been no simple and effective treatment. Since January 1983 we have treated all patients in our institution sustaining extravasation by a cytotoxic drug with a combination of DMSO and alpha-Tocopherole. During the first 48 hr after extravasation a mixture of 10% alpha-Tocopherole acetate and 90% DMSO was topically applied. The bandage was changed every 12 hr. So far eight patients with extravasation of an anthracycline or Mitomycin were treated on this protocol. No skin ulceration, functional or neurovascular impairment occurred in any of these patients. The only toxic effect observed by this treatment was a minor skin irritation. The combination of DMSO and alpha-Tocopherole seems to prevent skin ulceration induced by anthracyclines and Mitomycin.

Administration, Cutaneous↗

[Multiple myeloma].

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗

Unaltered immunocompetence in patients with non-disseminated breast cancer at the time of diagnosis.

Immunologic parameters were examined preoperatively in 104 patients with breast cancer, staged according to the TNM classification and in 95 age-matched healthy women. The immunologic evaluation in the peripheral blood included lymphocyte and monocyte counts, determination of E-rosette-forming T-lymphocytes (SER+) and B-lymphocytes (MER+), T-lymphocyte subsets defined with monoclonal antibodies (Leu-1, Leu-2a, Leu-3a) and with lectin fractionation (soybean agglutinin), lymphocyte transformation test with phytohemagglutinin (PHA) and concanavalin A (ConA), and colony formation of T-lymphocytes in agar (T-lymphocyte colony-forming cells, [TL-CFC]). Two age groups (Group A: 30-50 years; Group B: 51-70 years) and the different tumor stages (Stage I-IV) were analyzed. Patients and controls did not differ in the absolute numbers of lymphocytes, T- and B-cells. In patients of Group B, the absolute number of monocytes was increased slightly in Stage II and III and significantly in Stage IV (P less than 0.05). Similarly, the lymphocyte response to PHA was significantly reduced in Stage IV Group B only (P less than 0.05). ConA-induced lymphocyte proliferation and TL-CFC capacity were not different in patients and controls. In the small number of patients and age-matched controls in whom T-lymphocyte subsets were determined, the absolute numbers of T-cells with helper or suppressor phenotype as defined with Leu-3a, Leu-2a, or lectin fractionation with soybean agglutinin were similar. This study demonstrates that in patients with early breast cancer (Stage I-III), immunocompetence as defined by either functional in vitro studies or surface marker analysis is not significantly altered at the time of diagnosis. In contrast, patients with advanced disease (Stage IV) show a significant increase in the absolute number of monocytes and a depressed PHA responsiveness of mononuclear cells.

Adult↗

[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↗

Cytotoxicity of mitomycin C on clonogenic human carcinoma cells is not enhanced by hypoxia.

The bioreductive alkylating agent mitomycin C (mitomycin) has been shown to have greater activity under hypoxic than oxic conditions on murine cell lines such as the EMT-6 fibrosarcoma cell line. Solid tumors are known to contain hypoxic cells and are relatively resistant to ionizing radiation and some chemotherapeutic agents. We tested the cytotoxicity of mitomycin against fresh biopsies of human carcinomas under both hypoxic and oxic conditions in the human tumor clonogenic assay (HTCA). Additionally, we examined the metabolism of mitomycin by sonicates of the murine EMT-6 cells and the human WiDR colon carcinoma cells. We confirmed that under our clonogenic assay conditions the EMT-6 cell line was more sensitive to mitomycin under hypoxic than oxic conditions. Additionally, we established that EMT-6 cells also metabolize mitomycin at a more rapid rate under hypoxic than oxic conditions. However, these effects of hypoxia on mitomycin activity were not demonstrable for the human WiDR colon cancer cell line. In addition to these findings, the cytotoxicity of mitomycin was either unchanged or reduced under hypoxic conditions for ten fresh human tumors tested for mitomycin sensitivity in HTCA. Based on these observations, we conclude that the potentiating effect of hypoxia on mitomycin metabolism and biological activity may be peculiar to the murine EMT-6 and S-180 cell lines and that mitomycin C is not likely to have differential efficacy against hypoxic human carcinoma cells.

Animals↗

Reduced bisantrene-induced cytotoxicity and protein-associated DNA strand breaks under hypoxic condition.

The effect of hypoxia on bisantrene-induced cytotoxicity and protein-associated DNA strand breaks was studied in mouse L1210 leukemia cells, human T47D breast cancer cell line, and fresh samples of human tumor cells. For each cell type, there was enhanced cell killing under oxic versus hypoxic conditions (1-hour drug treatment at 37 degrees C). Likewise, in L1210 cells, the frequency of bisantrene (10 micrograms/ml for 1 hour)-induced protein-associated DNA strand breaks was reduced by 70% under hypoxic versus oxic conditions. The reason for enhanced cytotoxicity and DNA strand breakage in L1210 cells under oxic conditions could not be attributed to oxygen-enhanced cellular uptake of the drug. The clinical implication of these data is that bisantrene may be relatively ineffective against large tumors containing hypoxic cell populations.

Animals↗

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↗

Tumor growth stimulation in vitro by interferons.

Interferons (IFNs) are a family of polypeptides originally identified as antiviral substances. Subsequently, other properties of interferons were recognized, including inhibition of cell proliferation, and effects on the immune response and on expression of surface antigens. In this paper we present evidence that interferons, even the highly purified cloned IFNs, can stimulate clonogenic tumor growth in vitro. Of 225 human tumor (HT) samples tested with IFN in a clonogenic assay (HTCA), 30 (13.3%) showed growth stimulation (greater than 2 S.E. above control). The phenomenon was observed most frequently with acute myeloid leukemia (6/22 samples, 27.3%), and renal (2/10, 20%) and breast cancer (4/21, 19%), but significantly less frequent in melanomas (2/34, 5.9%). As an independent assessment of proliferation, tritiated thymidine uptake by tumor cells was measured autoradiographically in 21 patients with multiple myeloma. A significant increase of the thymidine labeling index was seen in 4 (19%) of the samples. Since this growth stimulatory effect was also observed with cell lines which lack any contaminating immunoreactive cells, there is strong evidence that interferons can directly stimulate the proliferation of clonogenic tumor cells in vitro. Growth stimulation by interferons occurred preferentially with lower dosages. It is important to be cognizant of potential clinical implications of tumor growth stimulation by interferons.

Cell Division↗

Simple and fast method to test the receptor for advanced glycosylated endproducts (RAGE) for its tumor suppressive potential using the Tet-On system.

The Tet gene expression system, that allows tightly controlled gene expression in response to doxycycline, was applied to analyze the influence of the receptor for advanced glycosylation endproducts (RAGE) on the growth of 293 cells in semi-solid medium. Establishing a Tet-On gene expression system involves two consecutive stable transfections. Here, we describe an alternative procedure to obtain a Tet-On gene expression system in a single transfection step for the use in tumor biology. The plasmids necessary for the regulated expression of RAGE together with the selectable marker plasmid were cotransfected in a molar ratio of 6:1. After aminoglycoside selection, 29 clones were analyzed using PCR revealing 8 colonies to be double stably transformed. Subsequent Western blot analysis showed inducible expression in 7 cell lines. Applying the one step protocol, the entire Tet-On expression system could be completed in half of the time required for the original two step method. The generated 293 double stable cells were used in the clonogenic assay for the testing of the tumor suppressive potential of RAGE.

Base Sequence↗