An automated pulse labelling method for structure-activity relationship studies with antibacterial oxazolidinones.

The 3-aryl-2-oxooxazolidinones are a new class of synthetic antibacterial agents that potently inhibit protein synthesis. An automated pulse labelling method with [3H]-lysine was developed with Bacillus subtilis to obtain additional quantitative activity data for structure-activity relationship studies with the oxazolidinones. Inhibition constants were calculated after a Logit fit of the data into the formula: % of control = 100/(1 + e[-B(X - A)]), where B is the slope of the model, X is the natural log of the inhibitor concentration and A is the natural log of the inhibitor concentration required to inhibit protein synthesis by 50% (ln IC50). When substituents at the 5-methyl position of the heterocyclic ring (B-substituent) were NHCOCH3, OH or Cl, the correlation coefficient was 0.87 between the MIC and IC50 values (for all compounds with MICs less than or equal to 16 micrograms/ml). The D-isomers of DuP 721 (A-substituent = CH3CO) and DuP 105 (A-substituent = CH3SO) gave MICs of 128 micrograms/ml and IC50s of greater than or equal to 50 micrograms/ml for protein synthesis, showing that only the L-isomers were active. By MIC testing, oxazolidinones with the B-substituent of NHCOCH3 and the A-substituent of CH3CO, NO2, CH3S, CH3SO2 or (CH3)2CH had comparable antibacterial potency; however, pulse labelling analysis showed that compounds with an A-substituent of CH3CO or NO2 were more potent inhibitors of protein synthesis.

Experience with and comparision of methods of reduction mammaplasty.

Experinece with bilateral reduction mammaplasty in 213 patients has been reviewed. Complications, while not infrequent, are rarely of a serious or lasting nature. In the experience of the authors, the McKissock procedure has yielded the most consistently good results, although very good results were occasionally achieved with all of the other techniques employed.

Experience with malignant melanoma of the head and neck.

Data on 127 patients with malignant melanoma who had a minimum 5-year follow-up have been analyzed. A good, though not yet significant, correlation appears to exist between length of survival and the diameter and the thickness of the primary lesion, the level of the tumor invasion, and the type of melanoma. A further analysis of patients with Stage I disease lends support to the use of "prophylactic" node dissection when the primary lesions penetrate to levels 4 or 5, or when they are 1.5 mm or greater in thickness. Our current overall approach to the management of malignant melanoma of the head and neck is outlined.