Short-term in vitro drug testing of mamma tumors: relation to estrogen and progesterone receptor levels, age, and proliferation rate.

The correlation between age, proliferation rate of tumors, estrogen and progesterone receptors, and in vitro chemosensitivity to Adriamycin was studied on 43 primary mamma tumors. From an univariate statistical analysis of the results, it appeared that sensitive tumors, unlike resistant tumors, have fewer estrogen receptors and show a higher proliferation rate. And in addition, they are blocked to a greater extent by Adriamycin. In both groups age and progesterone receptors were not significantly different. A multivariate statistical analysis showed that in the classification into sensitive and resistant tumors, the percentage remaining incorporation after addition of Adriamycin and the proliferation rate contributed 94 and 5%, respectively. The first variable was the best measure for in vitro chemosensitivity. The classification of the tumors with the aid of a discriminant function proved to be successful in 91% of all the cases. No significant difference was observed between the in vitro sensitivity to Adriamycin when patients were divided into two groups according to age (less than or equal to 50 and greater than 50 years; 64 and 45% sensitive, respectively). This indicates that all patients benefit from the treatment. It also appeared that 85% of the estrogen negative tumors were sensitive to Adriamycin. So a chemotherapeutic instead of a hormonal therapy has to be considered for all ages, particularly in the case of estrogen negative receptors.

Rapid assay for the in vitro chemosensitivity testing of human breast tumours. Control of assay conditions and quality assurance.

This study has been initiated by the definite need of a rapid, in vitro and patient-specific test to examine oncolytic drug effects on tumour cells. Therefore, we applied a test in which we monitored the incorporation of labelled nucleosides in isolated tumour cells, as a measure of nucleus activity (i.e. the Volm assay). A novel technique of erythrocytes co-precipitation has been developed and this enabled us to use a small number of tumour cells per test (200,000 cells/tube). During the assay, a strict pH control and a high starting viability have been introduced. A cytotoxic control and a t-test at two levels deal with the technical errors and the imprecision. For the evaluation of a specific drug a number of 1.8 million cells proved to be sufficient. Time-course studies of the incorporation of labelled nucleosides into isolated tumour cells have shown the optimal incubation time to be 2 h. The entire assay is completed within one day. HeLa cell cultures were employed as quality control material and criteria for interpretation have been developed. Preliminary results, based upon the evaluation of 43 human breast tumours with doxorubicin, indicate the correctness of the proposed procedures. In conclusion we can state that this assay not only provides useful information but above all that the results are made available in such a short time that they can be used directly in the medical management of the individual patient.

The classification of subjects with joint complaints on incomplete biochemical and haematological datasets.

We performed a retrospective study on 163 subjects suffering from rheumatic fever (16), rheumatoid arthritis (36), lupus erythematosus (17), gout (21), arthrosis (50) and osteomyelitis (23). The number of variables evaluated was 39. These were all of a general biochemical and haematological nature. A feature reduction resulted in sixteen variables that matched well with those known from the literature. Linear discriminant analysis yielded poor results in classifying the six disease categories (with 18 variables 61.8%). A reduction to three disease categories improved the classification results remarkably. This, and the excellent discriminating power between patients and the reference group, shows that the selected variables are illustrative only for general clinical pictures, such as infection, and not for the desired differential diagnosis.

The costing of tests in a laboratory for clinical chemistry and haematology.

The total cost of a haematology and clinical chemistry laboratory, including external and hospital costs, was studied in a district general hospital in The Netherlands. The main conclusion is that the number of samples analysed is the most important cost-setting factor, but that reduction in the number of requests does not result in the proportional diminution of costs.