Tumor-biological factors uPA and PAI-1 as stratification criteria of a multicenter adjuvant chemotherapy trial in node-negative breast cancer.

In axillary node-negative primary breast cancer, 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therapy is only needed for those 30% of node-negative patients who will relapse after primary therapy and eventually die of metastases. Traditional histomorphological and clinical factors do not provide sufficient information to allow accurate risk group assessment in order to identify node-negative patients who might benefit from adjuvant systemic therapy. In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1) in node-negative breast cancer patients. Based on these data, a prospective multicenter therapy trial in node-negative breast cancer patients was started in Germany in June 1993, supported by the German Research Association (DFG). Axillary node-negative breast cancer patients with high levels of either or both proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only. Recruitment was continued until the end of 1998, by which time 684 patients had been enrolled. Since then, patients have been followed up in order to assess the value of uPA and PAI-1 determination as an adequate selection criterion for adjuvant chemotherapy in node-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an impact on future policies in prognosis-oriented treatment strategies.

[Assessment of diagnostic lung function and diagnostic laboratory parameters in workers exposed to diesel exhaust below ground in comparison with non-exposed workers]. / Untersuchungen zur Beurteilung lungenfunktionsdiagnostischer und labordiagnostischer Parameter bei Dieselabgasexponierten unter Tage im Vergleich zu Nichtexponierten.

Toxic gases caused by the use of large Diesel-driven devices in underground mines may lead to impairment of health, especially in the respiratory system. By means of occupational hygiene supervision it may be checked if the effectiveness of accomplished occupational hygiene measures are sufficient. By an enlarged examination programme of the respiratory function and laboratory diagnostic investigation miners exposed to Diesel-exhaust-gas were compared within the above mentioned supervision with a non-exposed population. In this study was not found any difference between the respiratory results attributed to influence of Diesel-exhaust-gas. Among the laboratory parameters the exposition to Diesel-exhaust-gas will only affect the mercapturic acid, however, which also may be influenced by other factors. Under the conditions of the measured low degree of exposition was not found any correlation between the level of mercapturic acids and the duration of exposure as well as to the actual degree of exhaust-gas exposition.

Effects of experimental emotional stress and physical exercise on the circulation in hypertensive patients and control subjects.

Heart rate, intra-aortal blood pressure, cardiac output and peripheral vascular resistance were registered in 11 hypertensive and 11 normotensive subjects during exercise (up to 80 W on a bicycle ergometer), a semi-standardized interview concerning personal life situations, exposure to slides showing parents and marriage partners of the subjects, and during pressure on a hand ergometer. The blood pressure in all subjects increased during all these experimental conditions. During exercise this was associated with increases in heart rate and cardiac output and a decrease in peripheral resistance (hyperkinetic reaction). During the interview the heart rate and cardiac output also increased but to a lesser degree and in 15 of the 22 cases the peripheral resistance rose (predominantly hypertonic reaction). During the slide viewing the effects were similar to those of the interview but less marked. During the hand ergometer test the subjects showed a combination of the hyperkinetic and hypertonic response. Although there was a difference in their basal blood pressure and total peripheral resistance, these haemodynamic reaction patterns showed no difference between the hypertensive and normotensive subjects. These results support the hypothesis that essential hypertension is a quantitative 'exaggeration' of the same physiological processes which regulate the blood pressure in different situations in normotensive individual.