Suppression of Humoral Immune Responses by Dialkylnitrosamines: Structure-Activity Relationships

Suppression of Humoral Immune Responses by Dialkylnitrosamines:Structure-Activity Relationships. KAMINSKI, N. E., JORDAN, S.D., PAGE, D., KIM, B. S., AND HOLSAPPLE, M. P. (1989). Fundam.Appl Toxicol 12,321-332. Comparisons between chemical structureof N, N-dialkylnitrosamine congeners and their ability to alterthe Day 4 IgM antibody response to sRBC, body weights. and organweights of female B6C3F1 mice were investigated. Short-chainnitrosamine congeners were selected for these studies on thebasis of two criteria: (1) congeners wth symmetrical aliphaticchain length [N-nitrosodimethylamine (DMN), N-nitrosodiethylamine(DEN), N-nitrdipropylamine (DPN), N-nitrosodibutylamine (DBN)]and (2) congeners possessing an N-methyl group [N-nitrosomethylethylamine(MEN), N-nitrosomethylpropylamine (MPN), and N-nitrosomethylbutylamine(MBN)]. The immunotoxicity of each congener was evaluated basedon the compound's ability to suppress the in vivo sRBC antibodyresponse following 7 consecutive days of treatment. An ED50dose was calculated, using a linear regression analysis, foreach congener and represents the millimoles of congener perkilogram body weight required to cause a 50% suppression ofthe sRBC response. These studies demonstrated two general trends:(1) those dialkylnitrosamine congeners that possessed an N-methylgroup were most immunotoxic and exhibited comparable ED50 concentrations(42-183 µmol/kg); and (2) dialkylnitrosamine congenerspossessing symmetrical aliphatic chains demonstrated an inverserelationship between aliphatic chain length and immunotoxicpotency—DMN (62 µmol/kg) > DEN (276 µmol/kg)> DPN (467 µmol/kg) > DMN (1557 µmol/kg).Comparisons were also made between the immunotoxic potency ofvarious nitrosamine congeners in the whole animal and theirpotency in an in vitro hepatocyte-spleen cell coculture system.     

Quantitative Whole Body Autoradiographic Disposition of Glycol Ether in Mice: Effect of Route of Administration

Glycol ethers such as ethylene glycol monomethyl ether (EGME)are common solvents used in many industrial products. A largenumber of individuals are exposed to EGME through differentexposure routes. We investigated the differential distributionof EGME following various routes of administration using wholebody autoradiographic (WBA) techniques. Male B6C3F1 mice weretreated with tracer iv or oral doses of [2-¹⁴C]EGME.(4.05 µgEGME/kg equivalent to 0.8 mCi/kg) and euthanized at 1 and 24hr following treatment. In both groups of animals the highestlevels of radioactivity were detected in the liver, urinarybladder, bone marrow, kidney, and epididymis, at 1- and 24-hrtime periods. Computer-assisted quantitation of WBA indicatedthat there was markedly higher deposition of [2-¹⁴ and/or itsmetabolites in various tissues of the orally treated animalsthan in animals treated intravenously. Our studies also suggestthat [2-¹⁴C]EGME is rapidly distributed either from blood orstomach to various tissues. Preferential deposition of radioactivityin the peripheral tissues of the bone, with a progressive inwardaccumulation in the bone marrow, was observed. Selective permeabilityof EGME and/or its metabolites was indicated by the higher uptakeby the epididymis than that by testis. The high levels of radioactivityin biosynthetically active tissues, e.g., the liver, bone marrow,and gastric mucosa, is an indication of persistent interactionof the compound with cellular components of these tissues. Theseinteractions may lead to EGME toxicity.     

Physically restraining children for induction of general anesthesia: survey of consultant pediatric anesthetists

Objectives: To discover whether any consensus exists among the Association of Paediatric Anaesthetists of Great Britain and Ireland (APA) members regarding the use and acceptability (or otherwise) of physical restraint. Background: Despite growing recognition of children’s right to be consulted regarding their healthcare, the issue of how to proceed when faced with a child unwilling to undergo induction of general anesthesia remains relatively unaddressed. Methods: APA members were surveyed regarding their use or avoidance of physical restraint and alternate techniques to facilitate induction; factors affecting choice of technique; and extent of preoperative discussion. The anonymous online survey used both structured and free text responses. Results: Of 596 surveys, 310 were returned, a 52% response rate. Use of physical restraint and extent of restraint employed declines with increasing child age. Distraction techniques are frequently employed for children under 6 years, with the use of sedative premedication increasing as child age increases. Urgency of procedure, developmental delay, and preoperative discussion all have an effect. Comments demonstrated a wide range of views and lack of consensus on what constitutes physical restraint, and what degree of restraint, if any, is acceptable. Conclusion: Our results are similar to the US Society of Pediatric Anesthesia members, suggesting this remains an issue internationally. Consideration of practices in other specialties gives some guidance. Our survey shows a range of views as to what physical restraint is or involves, and what constitutes acceptable practice regarding the use or avoidance of physical restraint. We were unable to demonstrate consensus.     

SEVERE HEMOSIDEROSIS POST ALLOGENEIC BONE MARROW TRANSPLANTATION

Abnormal liver function persisting late after allogeneic BMT is usually attributed to chronic GvHD, viral hepatitis or drug toxicity. We describe a patient who had negative hepatitis serology, was on no hepatotoxic medication, had no evidence of GvHD but had abnormal liver function 15 months post MBT. She was diagnosed as having grade IV hemosiderosis of the liver. Her total red cell support had only been 52 units. We therefore postulate that in a proportion of patients receiving allogeneic BMT impaired intestinal iron absorption may be an important cause of hemosiderosis.