The importance of drug ionization for the action of calcium-antagonists and related compounds

pK-Values of Ca-antagonists and related cardiodepressive drugs have been measured by means of potentiometric microtitration. The presumable active species for all compounds investigated is the protonated molecule except nifedipine. This drug must exert its action via the uncharged form. From these results it could be concluded that protonization of ionizable nitrogen is one molecular prerequisite for voltage- or frequency dependence of action. Drug ionization does not correlate with the negative inotropic potency of the compounds investigated.     

Results of surgical treatment of 1028 cervical cancers studied with volumetry.

BACKGROUND AND METHODS. The clinical staging system of cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) entails a large measure of subjectivity. This study analyzed the results of 1028 patients with cervical cancer at three reference centers. All patients had radical surgery, and all surgical specimens were processed as histologic giant sections with precise volumetry of the tumor. RESULTS. The interpretation of the histologic findings of parametrial invasion, vascular involvement, and lymph node involvement was found to differ somewhat among the three centers. However, all these findings were associated with tumor size. Survival rates correlated more consistently with tumor volume than with clinical or histologic stage. Five-year survival rates ranged from 91% for patients with tumors smaller than 2.5 cm3 to 70% for those with tumors 10-50 cm3. The 5-year survival rate of 24 patients with tumors larger than 50 cm3 (71% of whom had lymph nodes with positive findings) was 48%. Survival rates were identical among the three centers for patients with tumors smaller than 10 cm3, despite different degrees of surgical radicality. In contrast, more radical surgery was associated with significantly better survival rates in patients with larger tumors. CONCLUSIONS. The results of this study indicate that volumetry of the tumor permits a more accurate assessment of therapeutic results in patients with cervical cancer than does the FIGO classification. Pretherapeutic assessment of tumor volume is possible with magnetic resonance imaging. It seems that maximum parametrial resection is not necessary for patients with smaller tumors (smaller than 10 cm3), but truly radical surgery in patients with bulky tumors achieves better results than those usually expected in Stage IIb cervical cancer and at least comparable to those of radiation therapy.     

Double sucrose gap voltage clamp in cardiac muscle

In double sucrose gap voltage clamp experimetns on frog atrial bundles the configuration of membrane current and contraction was used to estimate the quality of voltage control. Attention was focused on possible action potential activity along the test segment in response to depolarizing clamps. At low depolarizations large Na+ inward currents were observed while any tension response was missing. Transmembrane potential threshold for generation of a mechanical response was evaluated from conditioned (attenuated) action potentials. The mechanical threshold determined from action potential measurements was only slightly higher than that determined from step-clamp depolarizations. With clamp potentials below the threshold, then, any action potential activity induced by the inward current phase is expected to be rudimentary.