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Biomedical subjects

L Edler

Publications and source records attributed to L Edler.

At least 55 records · Page 3Linked to original sources
PubMed1987

[Remission in phase II and phase III studies: criteria and prerequisites].

We identify factors of influence for the observed variability of published rates of remission and we derive from these findings prerequisites and criteria for the assessment of remission in cancer therapy. As a consequence we postulate a separate assessment of patients with measurable and with non-measurable disease and a complete documentation of those patient characteristics in order to compare rates of remission of different studies. Several methods for the determination of sample sizes in phase II and phase III clinical trials are presented and discussed.

Antineoplastic Agents↗
PubMed1986

Xeroderma pigmentosum patients from Germany: repair capacity of 45 XP fibroblast strains of the Mannheim XP Collection as measured by colony-forming ability and unscheduled DNA synthesis following treatment with methyl methanesulfonate and N-methyl-N-nitrosourea.

A total of 45 XP fibroblast strains from the Mannheim XP Collection (representatives of XP complementation groups A, C, D, E, F or G, I, and XP variants) were investigated for colony-forming ability (term: D0) after treatment with up to ten doses of the methylating carcinogen MeSO2OMe. As controls 16 fibroblast strains from normal donors were used. Except for 4 XP strains (1 from group C and 3 from group D) which, however, were borderline cases, none of the remaining 41 XP strains was found to be more sensitive than normal controls. This held true within the limits of an experimental accuracy (experimental variability of D0 values) of +/- 7%. When weighted means were calculated for XP complementation groups and compared with that of normal donors at a significance level of 5%, no significant difference was detected. In contrast, after exposure of 6 XP group D strains to MeNOUr, a weighted mean D0 value was obtained which was significantly decreased by 27%. Unscheduled DNA synthesis (term: G0 which serves as a measure of excision repair) after exposure to MeNOUr was quantitatively the same (experimental variability: +/- 8%) both in the group of normal strains and in most of the XP complementation groups. Exceptions were group E and group F (or G) which had higher, and group I which had lower repair. Analogous G0 values measured after exposure to MeSO2OMe (experimental variability: +/- 13%), however, differed from that of the control strains: they were lower in XP complementation groups A, D, E, F (or G), and I. However, groups A, E, F (or G), and I including only 3 individual strains or less may be considered to be possibly ill-represented. Yet, group D including 11 XP strains did show reduction of the mean G0 value by 35%. From this it is concluded that there are repair defects in XP group D strains with regard to MeSO2OMe-induced adducts. These defects seem to be small.

Alkylation↗
PubMed1986

Prognostic factors of advanced colorectal cancer patients.

The cooperative oncology group for Chemotherapy of Gastrointestinal Tumors (CGT) retrospectively examined 139 patients with metastatic colorectal cancer for prognostic factors. Clinical characteristics, tumor parameters, and blood parameters were investigated for prognostic explanation of survival from the start of chemotherapy for the advanced disease. A combination of a univariate regression and a multivariate step down procedure with Cox's regression model led to the identification of performance status, sex, white blood count and, to a lesser degree, blood sedimentation rate and albumin as important prognostic factors. Based on these variables an individual risk score was calculated for each patient.

Colombia↗
PubMed1986

Establishment and growth kinetics of the mutant Ehrlich-Lettré ascites cell strain HD33 in permanent suspension culture.

Cells of a mutant in vivo subline of the Ehrlich-Lettré mouse ascites tumour (ELAT) were converted to growth in suspension culture. Kinetic analysis revealed the selective character of the conversion process; without a detectable adaptation period, a fraction of about 2 X 10(-5) of the explanted cells continued to grow in vitro. The resulting, mutant Ehrlich-Lettré ascites cell strain was designated HD33 and propagated uninterruptedly from 1974 on. The corresponding in vivo ELAT subline HD33 was derived from the HD33 ascites cell strain by intraperitoneal retransplantation. In HD33 cell suspension cultures, the population doubling time, the average intermitotic interval, as determined by videomonitoring, and the average duration of the cell cycle, as determined from percentage of labelled mitoses (PLM) data, were all measured at 15 hr. Cell loss and quiescent compartments were insignificant. The duration of the G1 phase was effectively zero. Both PLM data and [3H]/[14C] thymidine double-labelling measurements revealed an S-phase duration of between 11 and 12 hr. The G2 phase lasted 3-5 hr. The HD33 strain differs from comparable suspension strains of wild-type Ehrlich ascites cells in the insignificant role of density-dependent inhibition in growth, and the striking prolongation of the S phase which is associated with an excessive, cytoplasmic storage of glycogen by the mutant cells.

Animals↗
PubMed1986

Prospective randomized trial concerning hyper- and normoprolactinemia and the use of bromoergocryptine in patients with metastatic breast cancer.

This prospective trial was designed to help in selecting therapy for patients with elevated and normal plasma prolactin. Ninety-two patients entered this trial, of whom 86 were evaluable for final analysis. Hyperprolactinemic patients (n = 31) were randomized to receive VAC/FMC chemotherapy with or without bromoergocryptine. Normoprolactinemic patients with 'low risk' metastatic disease (disease-free interval greater than 30 months, ER/PR positive or unknown) were treated with medroxyprogesterone acetate or VAC/FMC chemotherapy. Normoprolactinemic 'high risk' patients (n = 42) (disease-free interval less than 30 months, EP/PR negative) received VAC/FMC chemotherapy with or without medroxyprogesterone acetate (MAP). The results show that bromoergocryptine does not improve response rate, duration of response and survival. Median survival of patients with elevated basal plasma prolactin (greater than 15 ng/ml) is reduced to 9 months compared to patients with normal basal plasma prolactin (17 months, log-rank p = 0.005). Unexpectedly, TRH stimulation proved inappropriate to separate normo- and hyperprolactinemic patients in terms of survival. Normoprolactinemic 'low risks' (tamoxifen failures) were observed to qualify for further hormone therapy (median survival 21+ months). Normoprolactinemic 'high risks' showed median survival of about 12 months with no apparent benefit for those receiving MAP, additionally. The results suggest that basal hyperprolactinemia, disease free interval, ER/PR receptor status, and liver metastasis are important prognostic variables. Endocrine and cytotoxic chemotherapy should be selected according to these risk factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The predictive role of delayed cutaneous hypersensitivity testing in postoperative complications.

Ten parameters, including delayed cutaneous hypersensitivity testing (DCH), were evaluated with regard to their predictive value in instances of postoperative septic complications. In 302 patients undergoing surgical treatment, 45 complications, including wound infection, abscess, pneumonia and sepsis, were seen postoperatively in 42 patients. When these patients were compared with 260 patients without complications, hemoglobin, leukocyte count, serum albumin, total protein, blood sedimentation rate, age and sex were found not to contribute to the prediction of postoperative complications. In DCH testing, the complication rate increased from 7.5 per cent in normergic patients to 20.6 per cent in anergic patients. With increasing length and severity of operation, the complication rate increased from 6.5 to 26.4 per cent and from 6.5 to 31.8 per cent, respectively. Only in severe, long lasting operations could DCH testing differentiate the complication risk. Normergic patients had a 8.6 per cent complication rate; hypoergic patients, 36.6 per cent, and anergic patients, 37.5 per cent. The results of DCH testing did not correlate with the complication rate in any of the other operative groups. In conclusion, the predictive value of DCH testing is clearly greater in groups of patients highly affected by the operative trauma. The results of this study show that it is important to consider both host defense mechanisms and environmental factors in the assessment of operative risks.

Adult↗
PubMed1985

Xeroderma pigmentosum patients from the Federal Republic of Germany: decrease in post-UV colony-forming ability in 30 xeroderma pigmentosum fibroblast strains is quantitatively correlated with a decrease in DNA-incising capacity.

A total of 16 normal and 46 XP fibroblast strains from the Mannheim Collection were investigated for colony-forming ability following exposure to both UV light and the "UV-like" carcinogen (Ac)2ONFln. The dose-response experiments included up to 13 dose levels. The exponential segments of the curves were analysed by linear regression and the negative reciprocal of the regression coefficient (D0) was calculated for each cell strain. For quantitating the DNA-incising capacity, DNA elution curves were determined at several UV dose levels. Plotting the initial velocities of the elution curves versus the UV dose yielded a regression line, the slope of which was used to obtain the characteristic value E0. Comparing D0 with E0 values showed that cell strains in which colony-forming ability was reduced suffered a reduction of DNA-incising capacity of the same magnitude. There were only 3 exceptional strains in which reduction of DNA-incising capacity was less pronounced than reduction of colony-forming ability. We have previously shown (Fischer et al. 1982) that D0 values from 27 XP strains of the Mannheim Collection were correlated with clinical symptoms. This correlation is now being extended by relating colony-forming ability to the magnitude of the DNA incision defect. From our data we conclude that the best quantitative biochemical denominator to explain the sun sensitivity of XP is that of a defective incision of UV-damaged DNA. A considerable similarity in sensitivity towards both UV light and (Ac)2ONFln was found in 16 normal and 46 XP strains. This seems to indicate that UV- and (Ac)2ONFln-induced DNA damage are removed to a large extent by the same pathways in human fibroblasts.

Acetoxyacetylaminofluorene↗
PubMed1985

A ninth complementation group in xeroderma pigmentosum, XP I.

A new complementation group of excision-deficient xeroderma pigmentosum (XP) is described in 2 patients living in the F.R.G. Dermatological, ophthalmological and neurological symptoms of XP are presented together with DNA repair characteristics such as unscheduled DNA synthesis, colony-forming ability and alkaline elution studied in cultured fibroblasts. The results are compared to normal controls.

Adolescent↗
PubMed1985

Computational statistics for cell survival curves. I. Evaluation of the colony-forming ability of a single cell strain by the APL function CFALINE.

An interactive program for the statistical analysis of cell survival curves by a linear regression approach is described. It allows for the computational determination of the linear part of a cell survival curve and the determination of a common slope estimate in the presence of repeated experiments for a particular cell strain with the appropriate variance estimates and confidence intervals.

Biometry↗
PubMed1985

An investigation of the adequacy of a randomization.

A randomization actually performed in an individual-based double-blind intervention trial in cancer epidemiology is investigated concerning the resulting imbalance of treatment assignment. Complete randomization, permuted block procedures, and adaptive urn models are simulated in order to assess how representative the achieved distribution is for the procedure used and how other procedures would have performed on the given study population. The achieved randomization is deemed to be satisfactory and the different procedures are discussed in light of different logistic requirements. It is argued that such investigations should be carried out when debating the implications of a given randomization.

Adult↗
PubMed1984

Combination chemotherapy (VAC/FMC) with immunostimulation in metastatic breast cancer: a randomized study comparing different times and routes of administration of Corynebacterium parvum.

From January 1978 to December 1980, 222 patients with metastatic breast cancer were included into a prospective multicenter trial. All patients were treated once a month with six cycles of VAC- (vincristine, adriamycin, cyclophosphamide) chemotherapy, followed by FMC (5-fluorouracil, methotrexate, cyclophosphamide) until progression was documented. By random assignment, the patients received immunostimulation with Corynebacterium parvum (CP) by one of four methods: subcutaneous (SC) on either day 1 or day 14, intravenous (IV) on either day 1 or day 14. The 214 evaluable patients were equally distributed to the four arms. The rates of complete or partial response to VAC/FMC plus CP did not differ significantly between the treatment groups. Of our patients, 22-33% were definite treatment failures. The Kaplan-Meier curves of duration of remission (medians 14 vs. 9 vs. 13 vs. 11 months) did not differ significantly. Only small differences in survival were noted among the four study groups (medians 15.4 vs. 17.5 vs. 17.2 vs. 13.0 months). However, complete and partial responders lived significantly longer (Log rank test P = 0.008), when CP was given on day 14 by the SC rather than IV route (29+ vs. 14.3 months). Patients in the four study groups were treated with virtually identical doses of VAC/FMC chemotherapy. Patients receiving CP intravenously on day 14 experienced significantly lower mean leukocyte counts than patients in the other groups. Many patients suffered from high temperature (requiring treatment with antipyretics) and severe gastrointestinal toxicity, particularly when CP was given IV on day 1 together with the chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Treatment of autochthonous rat colonic adenocarcinomas with a thioether-lysophospholipid derivative in mono- and combination chemotherapy.

In 361 Sprague-Dawley rats autochthonous colorectal carcinomas were induced by intrarectal application of the carcinogen AMMN. Tumor-bearing animals were treated with a synthetic thioether-lysophospholipid (TLP) derivative and in combination chemotherapy with 5-fluorouracil (5-FU) and carmustine (BCNU). There was no difference in the survival time of treated and untreated animals. The median large-bowel tumor weight was significantly lower in the TLP/5-FU and TLP/5-FU/BCNU combination therapy groups than in the control groups. Transient hepatotoxicity was observed in the high-dosage (50 mg/kg body weight twice weekly) TLP group. This study confirmed the relative resistance of AMMN-induced colorectal carcinomas to antineoplastic treatment.

Adenocarcinoma↗
PubMed1984

A two-sample censored-data rank test for acceleration.

A score test for the null hypothesis of proportional hazards against rank-regression alternatives is proposed as a complement to the logrank test for comparing censored survival curves. The test statistic has an asymptotic normal distribution that is independent of the logrank distribution under the null hypothesis, and its power is good against acceleration alternatives (i.e. with crossing hazards) where the logrank test fails. Monte Carlo studies indicate that its small-sample properties are comparable to those of the logrank and ranksum procedures.

Biometry↗
PubMed1983

Spontaneous in vitro malignant transformation in a xeroderma pigmentosum fibroblast line.

This paper deals with a spontaneous malignant transformation in one of our XP fibroblast lines. This cell line, designated XP29MA, was derived from a 14-year-old boy who did not show skin tumors or precancerous alterations either at the time of clinical examination or when the biopsy was taken. We have compared the following features in both the malignant and the benign cell line from which the malignant line developed: tumor formation in nude mice, repair capacity, cytogenetic status, light and electron microscopic characteristics. The benign cell line XP29MA had a doubling time of 4.3 d, did not form tumors in nude mice, showed a very low repair capacity (as determined by colony-forming ability, unscheduled DNA synthesis and alkaline elution) but exhibited a normal cytogenetic and ultrastructural status. In contrast, the transformed cell line XP29MAmal grew three times faster, formed colonies in methyl cellulose, gave rise to fibrosarcomas in nude mice, showed a drastically higher repair capacity, and was characterized by an extreme genetic imbalance, resulting from numerical and structural chromosome alterations of Nos. 1, 3, 4, 8, 12, 16, 17, 18, 20 and 21. Ultrastructural examination revealed fusiform and polygonal cells, the latter exhibiting large indented nuclei, vesicular dilatations of the endoplasmatic reticulum and numerous lysosomes. The higher repair capacity in XP29MAmal cells is tentatively explained in terms of reversion, enhancement of post-replication repair and/or expression of SOS-type functions.

Adolescent↗
PubMed1983

Computational methods for the screening of pharmacokinetic parameters in metabolism experiments.

A computational strategy is presented which is useful for the qualitative and quantitative assessment of reaction-kinetic parameters in a one-compartment open model for the metabolism of substances in a biological system, especially the metabolism of dialkylnitrosamines to the ultimate carcinogen. The mathematical model used is that of first order kinetics and results in Bateman-functions. The strategy allows to decide about stability or instability of a substance occurring in a chain of transformations. In the case of stability quantitative estimates of the half life are provided. The procedure compares parameter estimates from models of different qualitative nature. These estimates are derived by linear or non-linear regression methods.

Biotransformation↗