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Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 199 records · Page 11Linked to original sources
PubMed1992

Local hyperthermia enhances cyclophosphamide, ifosfamide and cis-diamminedichloroplatinum cytotoxicity on human-derived breast carcinoma and sarcoma xenografts in nude mice.

Antitumour response and toxicity of locally applied hyperthermia with or without cyclophosphamide, ifosfamide, and cis-diamminedichloroplatinum (cisplatin) have been compared. The model systems were human breast carcinoma (MX1/3) and human sarcoma (S117) grown in nude mice. In order to detect changes of tumour oxygenation intratumoral PO2 and pH were measured before, during and following hyperthermia. In both human tumour lines a monotherapy with one of the cytotoxic drugs or with hyperthermia caused a transient growth delay, while the combination of the same dose of the drugs with hyperthermia (at 43 degrees C for 1 h) resulted in complete tumour remissions. During hyperthermia, in both tumour types oxygenation was improved. Intratumoral pH remained practically unchanged.

Animals↗
PubMed1992

Hyperthermia enhances mitoxantrone cytotoxicity on human breast carcinoma and sarcoma xenografts in nude mice.

In this preclinical in vivo study, we measured antitumor response, local side effects and systemic toxicity of locally applied water-bath hyperthermia given alone or simultaneously with mitoxantrone (3 mg/kg b.w. i.v.; LD 10) on a human derived breast carcinoma (MX 1) or a human sarcoma (S 117) transplanted to female athymic (nude) mice. A single hyperthermia treatment at a tumor temperature up to 43 degrees C for 1 hr caused in both tumor lines only minor tumor regressions and transient tumor growth delay. However, the antitumor effect of mitoxantrone was significantly enhanced by local hyperthermia at 42 degrees C and particularly at 43 degrees C. In both tumor lines complete tumor regressions were achieved only if mitoxantrone was combined with hyperthermia. Undesired side effects and drug toxicity were not enhanced by hyperthermia. According to in vitro data and the results of the present in vivo study mitoxantrone seems to be a good candidate for clinical trials in combination with locoregional hyperthermia.

Animals↗
PubMed1992

[Adrenal cortex carcinoma. A rare cause of a Conn syndrome in childhood].

A 2 1/3 year old girl presented classical Conn-Syndrome as diagnostic feature of an adrenocortical carcinoma. Sonographic diagnosis was confirmed by CT-scan, typical hormonal pattern and subsequent surgical procedure. Without further therapy there has been no relapse with a follow-up of 3 years.

Adrenal Cortex Hormones↗
PubMed1992

Fluorouracil versus folinic acid/fluorouracil in advanced colorectal cancer--preliminary results of a randomized trial.

Patients with advanced colorectal cancer were randomized to receive either fluorouracil (5-FU) 370 mg/m2 IV days 1 to 5 followed by weekly applications of 5-FU 600 mg/m2 or the same doses of 5-FU preceded by folinic acid 200 mg/m2. Because of toxicity, the weekly 5-FU dose in the combination treatment schedule was reduced to 500 mg/m2 in the course of the study. As of November 1990, 135 patients entered the study; 71 have received combination therapy, and 64 monotherapy. Sixty-three and 59 patients, respectively, are included in the present interim analysis. The two groups are well matched for age, performance status, site of disease, number of metastatic sites, and biochemical parameters. Treatment results are evaluable in 118 patients. Thirty percent receiving combination treatment and 20% receiving monotherapy achieved a complete or partial remission. There is no survival time difference between the groups. However, time to progression is superior in the combination treatment group (median 26 weeks compared with 13 weeks). The main toxicity was diarrhea during the weekly therapy. This was especially true for patients receiving combination treatment before the reduction of 5-FU dosage. In contrast to only four of 56 patients with monotherapy, 14 of 39 with the combination treatment at the initial dosage had severe diarrhea with two treatment-related deaths in this latter group. By reduction of 5-FU dosage during the weekly therapy severe diarrhea could be clearly reduced with only one of 18 patients suffering from diarrhea of World Health Organization grade 3. Other toxicity was usually mild. In conclusion, a prolongation of time to progression could be achieved by combination treatment of folinic acid and 5-FU, which was well tolerated when the weekly dose of 5-FU did not exceed 500 mg/m2.

Colorectal Neoplasms↗
PubMed1992

[Osseous leiomyoma--a first-time description].

In a 54-year old housewife presenting with left hip pain due to a circumscribed intraosseous lesion of the femoral neck, histological assessment following resection showed a benign intraosseous leiomyoma. Years ago a diagnosis of disseminated peritoneal leiomyomatosis had been made.

Bone Transplantation↗
PubMed1991

Enhanced repair of O6-methylguanine DNA adducts in the liver of transgenic mice expressing the ada gene.

The capacity to repair O6-methylguanine-DNA adducts was measured in the liver of transgenic mice expressing a chimeric gene consisting of the inducible P-enolpyruvate carboxykinase (GTP) promoter linked to the bacterial O6-alkylguanine-DNA alkyltransferase (ada) gene. Under induced conditions, total hepatic alkyltransferase reached 32.8 +/- 4.2 (SE) fmol/micrograms DNA compared to 7.8 +/- 1.1 fmol/micrograms DNA in nontransgenic mice. Administration of methylnitrosourea or nitrosodimethylamine to both groups of mice produced O6-methylguanine-DNA adducts which resulted in repair-mediated depletion of total hepatic alkyltransferase in a dose-dependent fashion. In nontransgenic mice, depletion of hepatic alkyltransferase occurred at lower doses of carcinogen, and recovery of alkyltransferase activity occurred later than in ada+ transgenic mice. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of residual alkyltransferase activity after methylating agent exposure indicated that the bacterial as well as endogenous mammalian alkyltransferases were functioning as DNA repair proteins in hepatocytes in vivo. Analysis of O6-methylguanine- and N7-methylguanine-DNA adducts in the liver of transgenic and nontransgenic mice after treatment with one dose of 50 mg/kg methylnitrosourea i.p. revealed that transgenic mice repaired in situ O6-methylguanine-DNA adducts approximately 3 times faster than nontransgenic mice, commensurate with the increase in alkyltransferase activity. Thus, ada+ transgenic mice treated with methylnitrosourea have lower levels of persistent mutagenic O6-methylguanine adducts than ada- nontransgenic mice. Hepatic expression of bacterial alkyltransferase appears to protect mice from the DNA-damaging effects of N-nitroso compounds in vivo.

Animals↗
PubMed1991

Separation of clonogenic and differentiated cell phenotypes of ovarian cancer cells (HOC-7) by discontinuous density gradient centrifugation.

We isolated clonogenic cells from differentiated HOC-7 ovarian cancer cells. Both cell subsets were characterised in respect to morphology, growth behaviour, DNA content and expression of tumour-associated antigens and nuclear oncogenes. Ten cell fractions (Fr) were separated by centrifugation in a discontinuous density gradient (Fr 1 less than 1.037 g/ml to Fr 10 greater than 1.069 g/ml, steps 0.004 g/ml). Large adenoid cells containing vacuoles filled with neutral polysaccharides were concentrated in Fr 1-4. These cells were non-clonogenic in soft agar. The growth on solid substrate was highest in Fr 6 and 7, intermediate in Fr 2-5 and Fr 8-10 and lowest in Fr 1. The mean cloning efficiencies of the fractions in soft agar were highest in Fr 6 (8.1%) and lowest in Fr 2 and 3 (0.1%). Diploid and near tetraploid cell subsets were found with similar frequency in all fractions. Immunocytochemistry revealed 4-7% Ki-67 positive cells in Fr 1-6 and 12-20% in Fr 7-10. In Fr 3-10 greater than or equal to 79% of the cells expressed CA 125. Positivity for c-myc, c-myb and c-fos (greater than or equal to 74%) was not correlated with clonogenicity. In conclusion, differentiated cells (Fr 1-4) were separated from cells with higher growth rates (Fr 5-10). Clonogenic cells were enriched in Fr 6. These data indicate that discontinuous density gradient fractionation represents a useful method for separation of cells with different degrees of differentiation, growth potential and clonogenicity.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

Pharmacokinetics and metabolism of cyclophosphamide administered after total body irradiation of bone marrow transplant recipients.

High-dose cyclophosphamide is used immediately after total body irradiation (TBI) in conditioning for bone marrow transplantation (BMT). Possible interactions of the two treatment modalities were sought by measuring the blood pharmacokinetics of CP and 4-hydroxy-cyclophosphamide (4-HOCP) in patients undergoing BMT. There was a non-significant trend to a shorter half-life of CP compared to reported values. Exposure to 4-HOCP, the major metabolite of CP, did not appear to be altered by prior TBI of the patient.

Adolescent↗
PubMed1991

Metabolism and pharmacokinetics of oral and intravenous ifosfamide.

The initial metabolism of ifosfamide (IF) consists of two different pathways: enzymatic hydroxylation at carbon-4 forms the cytostatically active metabolite 4-OH-IF ("activated ifosfamide") whereas side-chain oxidation results in the liberation of chloroacetaldehyde, a compound with possible neurotoxic properties. The pharmacokinetics of ifosfamide and its activated form were investigated in 12 cancer patients, who received both oral and i.v. treatment in a randomized sequence on days 1 and 3 at a dose of 1 g/m2 (n = 7) or 1.5 g/m2 (n = 5). In 3 patients the pharmacokinetics of chloroacetaldehyde were also investigated. After oral application, ifosfamide absorption proceeded rapidly, the oral bioavailability was 0.92. Independent of the route of ifosfamide application on day 1, the terminal half-life on day 3 (when the drug was given by the alternative route) was decreased in 6 out of the 12 patients, thus indicating self-induction of hepatic metabolism. 4-OH-IF was already present 20 min after ifosfamide administration. In the individual patient the concentrations of 4-OH-IF were always higher after oral than after i.v. IF application: the mean p.o.:i.v. ratios for cmax and the area under the concentration/time curve were 2.3 and 1.7 respectively (P less than 0.05). In a first series of 3 patients the chloroacetaldehyde concentrations measured after oral ifosfamide application were about twice as high as those when the drug was given intravenously. These results indicate that (in comparison to the i.v. route) orally administered ifosfamide may be more cancerotoxic but also leads to higher levels of chloroacetaldehyde. This would explain the neurotoxic side-effects previously seen after oral administration of comparatively low ifosfamide doses.

Acetaldehyde↗
PubMed1991

Effects of hyperthermia and/or hyperglycemia on pH and pO2 in well oxygenated xenotransplanted human sarcoma.

The heat-induced interdependent changes of tumor blood flow, pO2, and pH decisively influence the therapeutic effect of hyperthermia (HT). This fact has induced us to determine simultaneously the frequency distribution of local pO2 values and the intratumoral pH in a xenotransplanted human sarcoma cell line at a normal blood glucose level and under hyperglycemic conditions before, during, and after HT. Two groups, one of 10 and one of 9 congenitally athymic nude rats with a subcutaneously implanted S117 human sarcoma into the right hind paw (mean tumor volume 5.3 cm3) were treated with local waterbath HT (tumor temperature 43 degrees C, 1 hr) alone or in combination with i.p. glucose injections (6 g/kg, 2 hr before the onset of HT). Tumor oxygenation remained improved throughout HT. Tumor pH did not decrease during HT. Hyperglycemia alone elicited a decrease of intratumoral pH and pO2, probably mainly due to hemoconcentration. The additional warming of the tumors (43 degrees C) during hyperglycaemia did not further decrease pO2 and pH. Silver stained sections of the tumors showed only a few very small necrotic areas, even in tumors of volumes up to 8 cm3. Our results indicate a well oxygenated tumor. In contrast to most tumors studied so far, hyperthermia in this tumor induces not only an initial increase of oxygenation but a lasting elevation of mean tumor pO2 for the duration of HT (up to 60 min).

Animals↗
PubMed1991

[Histiocytosis X (eosinophilic granuloma) of the caruncle].

The lacrimal caruncle of an 11-year-old female patient developed a 2 mm x 3 mm-sized growth with the primary appearance of an abscess. The process did not regress under local antibiotic therapy and was excised. Histological examination revealed histiocytosis X (eosinophilic granuloma).

Child↗
PubMed1991

[The effect of hadacidin, ultraviolet irradiation of blood (UVB) and thiamine on the prenatal development of Uje:WIST rats: correlation with the hepatic activity of gamma-glutamyltranspeptidase (GGT)].

The influence of hadacidin, a model substance for induction of cheilognathouranoschisis in rat fetuses (2,550 mg/kg b.m. at gestation day 12), ultraviolet irradiation (UVB) of blood (1 week before gestation) and thiamine (25 mg/kg b.m. from gestation days 12 to 15) on the prenatal development of rats at the 20th day of gestation was investigated. Using the body mass and the hepatic GGT-activity as parameters. Hadacidin caused a distinct retardation of the fetal somatic development. Partially, the embryotoxic effect was compensated by UVB or thiamine. The combination of both procedures was more effective. There is a good correlation between the maturation grade of fetuses at day 20 of gestation and the hepatic GGT activity.

Animals↗
PubMed1991

[Influence of ignorance of caries prevention on tooth health and behavior of junior high students].

Within the framework of an averaging study (clinical examination combined with written questionnaire) an attempt was made to determine the extent to which theoretical and practical knowledge of caries prophylaxis influences the behaviour and dental health of school children. Mean DF and DMF levels, it was demonstrated, are significantly reduced in children who know more; also, a higher percentage of children reported brushing their teeth more than once a day. In spite of this, a considerable discrepancy is noticed between knowledge and behaviour. Improved integration of dental hygiene instruction in the school day could improve school children's motivation to change their behaviour on a lasting basis.

Adolescent↗