Effectiveness of systemic BCG therapy in advanced melanoma.

The effect of systemic BCG therapy on advanced melanoma was studied in 42 patients with stage II and stage III disease. Evaluation of the immune response prior and during therapy revealed that patients who failed to convert a negative purified protein derivative (PPD) reaction and those having a low stimulation ratio of lymphocyte cultures had rapidly progressive disease and short survival. Neither tumor regression nor prolongation of survival could be appreciated in patients with stage III disease. Furthermore, aggravation of symptoms was observed in patients with visceral metastases. Fifty percent of the patients with stage II melanoma treated by operation and adjuvant immunotherapy had recurrent or metastatis disease within two years. No adverse effects were noted in patients with early disease who received adjuvant therapy. Two patients who had a full course of systemic BCG therapy developed severe reactions after intralesional injection of the vaccine. Further experience with various immunotherapeutic regimens and longer follow-up are necessary to evaluate its value in the early stages of melanoma.

Multiple molecular forms of human alanine aminopeptidase: immunochemical properties.

Human pancreas, kidney, and liver alanine aminopeptidases have similar if not identical antigenic determinants even though these three isoenzymes have distinctly different electrophoretic mobilities. Single precipitin lines without spur formation were obtained for all three enzymes with antisera obtained from rabbits immunized with these three purified enzymes. Treatment of these enzymes with neuraminidase eliminated the differences in their electrophoretic migration on polyacrylamide gels and on agarose immunoelectrophoresis gels. Treatment of the pancreas, kidney, and liver alanine aminopeptidases with their respective antibodies yielded enzymes that displayed non-competitive inhibition when the dependence of velocity upon substrate concentration was determined for each enzyme, i.e. the antibodies did not cause a change in the Km values obtained in the absence of the antibody whereas kcat was reduced to the same extent for each enzyme. The removal of sialic acid(s) from these enzymes did not alter their immunochemical characteristics or their kinetic characteristics.

A kininase and a kinin-converting enzyme: two distinct alpha aminoacyl peptide hydrolases from bovine lung.

Two closely related but different aminopeptidases from bovine lung have been isolated and characterized. The first aminopeptidase, which removes the N-terminal arginine residue from L-arginyl-L-prolyl-L-proline, bradykinin, and des-[Arg9]-bradykinin, has kininase activity; it has a pH optimum of 8.0, is stimulated by Mn2+, and its molecular weight in dilute buffers is slightly greater than 240,000 daltons. The second aminopeptidase, which converts kallidin to bradykinin, has kinin-converting activity; it has a pH optimum of 6.8, is stimulated by Co2+, and its molecular weight in dilute buffers is 250,000 daltons. The kinin-converting enzyme is blocked from action when the N-terminal penultimate residue is proline.

Effect of alkali metal salts on Sarcoma I in A/J mice.

The chloride salts of lithium (Li+) and cesium (Cs+) were evaluated for their ability to influence the growth of Sarcoma I implants in A/J mice. The administration of daily doses of either 1 or 3 mEq/kg CsCl to these mice reduced the incidence and size of tumor implants. This effect was not apparent in animals receiving a smaller dose (0.5 mEq/kg) of the same drug. At the time of sacrifice the serum level of Cs+ in this latter group was approximately half that recorded in animals receiving the higher doses of CsCl. No effect on tumor incidence or rate of growth was observed in animals receiving different doses of LiCl. Because of the similarities that existed between cesium and potassium, it was postulated that the effect of cesium was due to alterations in the intracellular composition of the tumor cells. Also, the possible role of cytotoxic agents in potentiating the inhibitory effect of cesium on tumors was discussed.

Use of topical antiseptic in prophylaxis of catheter-related septic complications.

Pretreatment of catheters by a simple new procedure designed to reduce the incidence of septic complications was tested in both in vitro and in vivo studies. In the former experiments, the high sensitivity of gram-negative bacteria and fungi to Silastic (silicone rubber) catheters pretreated with silver nitrate solution was determined. The antimicrobrial activity remained unchanged after both sterilization and up to six weeks of storage. Furthermore, prolonged incubation of treated catheter segments in Escherichia coli inoculated plasma resulted in a significant reduction of organisms in the media and those adherent to the surface of the catheters. The in vivo experiments were performed upon two groups of rabbits. In the first group, catheters (one treated and one untreated) were implanted into contralateral jugular veins. In the second group, alternating treated and control catheter segments were threaded onto polyethylene core tubing; the resulting string of segments was positioned in the inferior vena cava. Five to 11 days after implantation of the catheter, all rabbits were intravenously injected with live E. coli (approximately 10(8) to 10(9) organisms per kilogram of weight); 18 to 24 hours later, the catheters and blood samples were removed for cultivation. Significant reductions in both incidence and magnitude of colonization in treated catheters by E. coli were observed in both rabbit groups. Additionally, histologic examination did not reveal any significant differences between contralateral jugular veins (previously in prolonged and intimate contact with the indwelling catheters), confirming the absence of any local adverse effects of silver nitrate.

The effects of varying fluid volume and rate of resuscitation during uncontrolled hemorrhage.

BACKGROUND: The role of rate and volume of infusion in survival from experimental uncontrolled hemorrhage was evaluated. METHODS: Hemorrhage was initiated using tail resection in 43 female rats assigned to the following five groups: nonresuscitated; resuscitated with moderate volume, slower rate; resuscitated with moderate volume, faster rate; resuscitated with high volume, slower rate; and resuscitated with high volume, faster rate. RESULTS: A trend toward improved survival was noted with faster rate of infusion (60 vs. 33.3% survival rate with moderate volume and 28.6 vs. 12.5% with high volume, compared with 16.7% in the nonresuscitated animals). CONCLUSION: Rapid infusion of moderate volume of isotonic saline improved survival in uncontrolled hemorrhage. Extreme volumes, infused rapidly, also resulted in higher survival rates compared with those observed in nonresuscitated rats.