Glucocorticoid-binding macromolecules in normal tissues and tumors. Stabilization of the specific binding component.
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Biomedical subjects
Publications and source records attributed to A F Kirkpatrick.
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STUDY OBJECTIVE: To determine the potential clinical significance of admixtures of thiopental sodium and acidic drugs, which are used during induction of general anesthesia and can cause the formation of particles of thiopental. DESIGN: Using an infusion setup similar to that used for a rapid-sequence induction of general anesthesia, injection of either pancuronium bromide or vecuronium bromide caused formation of particles of thiopental that were measured using a particle analyzer. The effects of delaying the injection of the muscle relaxant on particle formation and the effects of plasma on particle dissolution were studied. MEASUREMENTS AND MAIN RESULTS: The thiopental particles had a diameter of 17 to 39 microns, with a concentration of 15,000 to 20,000 particles/ml. Particle formation was prevented when a 30-second delay preceded administration of pancuronium or vecuronium following injection of thiopental. No particle formation was detected when succinylcholine was injected. Human plasma was far more effective than a crystalloid solution in dissolving thiopental particles. CONCLUSIONS: It is unlikely that clinically significant particles of thiopental will remain intact upon entering the bloodstream. However, mixing thiopental with pancuronium or vecuronium has the potential of disrupting intravenous access due to occlusion with particles.
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Lecithin-coated microdroplets of methoxyflurane (MOF) are shown to produce local anesthesia of three- to six-day duration in the skin with a single intradermal injection in rats. Anesthesia was quantitated by elevation of the threshold (milliampere) for shock vocalization with intradermal electrodes. Intradermal injection of 0.1 ml 0.5% MOF gave moderate (2.1 mA) anesthesia of approximately three-day duration for a 10-12-mm diameter area, with no damage to the tissue. Higher concentrations gave six-day duration anesthesia at very high level (7 to 12 mA) anesthesia of three- to five-day duration with some damage to the tissue. At 4.4% MOF, ulcers formed in the center of the injection site with maximal dimensions of 1.3 mm (11-13% of the site diameter). Phenol, a widely used neurolytic agent, was tested as a control in the same concentration range. Phenol at 4.4% gave very high level (8 mA) anesthesia for longer than seven-day duration and caused formation of ulcers with maximal dimensions of 3.8 mm (31-38% of the site diameter). Analysis showed that MOF produced less damage than phenol for any given degree of anesthesia. Systemic toxicity and pharmacokinetic data are also presented. Phenol produced a hypothermic reaction and behavioral changes, whereas MOF was without systemic effect. The plasma concentrations of phenol were four to five times greater than those of MOF. These results suggest that MOF may have clinical advantages over phenol.
Lecithin-coated microdroplets of methoxyflurane (MOF) have been reported to produce local anesthesia of long duration in rats. The present study was conducted in two phases. The first phase was open label studies in two human volunteers aimed at determining the effective concentration of MOF in human skin. Over the concentration range of 0.3-2.4%, MOF produced local anesthesia to pinprick and cold stimuli within 15 seconds. The duration of the anesthesia effect of 2.4% MOF in the skin of the buttock, forearm and leg was five to eight days. Microdroplets containing isoflurane, a more volatile agent, gave an anesthetic effect that reversed within two to five hours. In the second phase of the study, the safety and efficacy of MOF were compared to phenol in placebo-controlled and blinded studies using indwelling stimulating electrodes. Phenol was destructive to skin at a concentration necessary to obtain a degree of local anesthesia comparable to MOF. The greater part of the anesthetic effect produced by phenol at this "toxic" concentration was transient (approximately one hour). In contrast to phenol, MOF produced an anesthetic effect lasting four to seven days without producing visible damage to skin. These results suggest that MOF is safer and more efficacious than phenol for producing long-lasting local anesthesia of human skin.
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