Uses of streptomycin

Dr. Modell: The conference this afternoon was on the subject of the uses of streptomycin. The experiences with the sulfa drugs and penicillin have been put to good use in speeding up the steps necessary for the proper clinical evaluation of this new antimicrobial agent and now, only about three years after the first clinical reports on streptomycin, a formidable volume of information has accumulated concerning its actions and uses. The material is now available in a highly purified form. Since, however, it still contains some impurities, varying in amounts in different preparations, a biologic assay is applied to the different lots. It is less confusing to express dosage in units of weight rather than in biologic units and, therefore, the labels on the vials describe the contents in terms of Gm, of pure streptomycin base. Streptomycin is freely soluble in water. It is suitable for all the common routes of administration. Not enough is known about its absorption by oral administration and it does not seem to be useful for systemic action by the oral route. It is most commonly given by intramuscular injection in divided doses. A dose of 2 to 3 Gm. daily appears to be adequate for the majority of infections in which it is useful. Larger doses are likely to cause too high an incidence of toxic effects.Streptomycin is effective against most of the organisms which are inhibited by penicillin. In addition, however, it exerts a potent action against gram-negative organisms which are uninfluenced by penicillin. While bacteriologic experiments suggest a very wide field of usefulness for streptomycin, direct experience in the treatment of human diseases has greatly restricted the scope of its application. Experience thus far indicates that penicillin is preferable in those infections in which either of the drugs might be used because penicillin is non-toxic while streptomycin possesses toxic actions which are sometimes quite serious. There is also the fact that penicillin is administered in quantities measured in milligrams and streptomycin in quantities of grams and these large amounts of the drug are not practical for some of the special technics of administration such as suspension in wax and oil for delayed absorption. Thus far, streptomycin has been found especially useful in urinary infections caused by the Escherichia coli and some other, gram-negative bacterial infections of the urinary tract such as the Bacillus lactis aerogenes, Bacillus proteus and Bacillus pyocyaneus. It is highly effective in Friedländer's pneumonia, Hemophilus influenzae meningitis and tularemia. It has also been found effective in pneumonias, abscesses, peritonitis and other infections caused by the gram-negative bacteria frequently found in the urinary tract. It appears to be without value in virus infections. One of the most stirring aspects of streptomycin action is the observation that it cures certain forms of animal tuberculosis and the now well established clinical experience showing that it may check some forms of human tuberculosis, especially those in the exudative stage. There was considerable discussion in the conference concerning the details of its rôle in the therapy of human tuberculosis.Two other phases of streptomycin therapy received special consideration. There is some indication that different members of the same bacterial species show wide differences in susceptibility to streptomycin and it is now well established that for most infections, resistance to streptomycin is acquired quite rapidly, in a matter of days to weeks. This limits the application of the drug to brief courses of treatment and necessitates the use of fully effective doses, from the outset. The next point is the matter of toxicity. Streptomycin is not an innocuous drug. In addition to the various allergic drug reactions such as skin rash and fever, it may produce serious renal damage, it may affect the blood-forming organs and it exerts an action on the central nervous system involving the vestibular apparatus and the eighth nerve causing vertigo, tinnitus and impaired hearing, some of the effects becoming permanent. These effects are apt to occur after prolonged use of the drug, after three or four weeks. They are more frequent with the larger doses, doses larger than those usually necessary. One needs to keep them in mind, however, for the full scope of the applications of streptomycin has not yet been established and a good deal of exploration is still necessary to establish the full potentialities of streptomycin in human infections. In the present state of our knowledge, there is justification in giving streptomycin a trial in serious bacterial infections in which the other specific anti-microbial agents have failed. It is suggested that an in vitro test of the sensitivity of the organism may help to establish the indication for its trial in such cases.     

Do Electrode and Lead Design Differences for Permanent Cardiac Pacing Translate into Clinically Demonstrable Differences? (Comparison of Sintered Platinum and Activated Vitreous and Porous Carbon Electrodes)

A randomized prospective study was undertaken to compare the electrical performances of three permanent, endocardial, tined pacing leads with different electrode designs--sintered platinum, vitreous carbon, and porous carbon. Ninety-nine patients received one of the leads (S80 31; 423S 32; S100 36). Acute R wave amplitude and ST elevation of the native endocardial electrogram, voltage threshold, impedance, and current flow at four pulse durations (0.25-1.0 msec) were measured. Voltage thresholds were measured noninvasively at each of four pulse durations at 2 days and 1, 3, and 6 months after implantation. No significant differences were found in sensing properties, or current flow at threshold at 0.5 msec pulse duration. The 423S lead had a significantly higher impedance at threshold and both a higher impedance and lower current flow at 5 V. No significant differences in threshold voltages were found between the three leads at any pulse duration, at any of the assessed times after implantation. Six-month thresholds for the S80, 423S, and S100 leads were 1.18 +/- 0.35, 1.17 +/- 0.29, and 1.06 +/- 0.38 V respectively at 0.5 msec pulse duration. Differences between 'high performance' pacing leads need to be of a greater order of magnitude before they can be exploited to give any real clinical advantage to patients.     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.