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.     

Clinical, biochemical and pathological features of initial and repeat transrectal ultrasonography prostate biopsy positive patients

BACKGROUND: Using sextant biopsy, 16-41% of prostate cancers were diagnosed on repeat biopsy. The objective of the present study was to compare the differences in the clinical, biochemical and pathological features between patients with positive results on initial and repeat biopsies, with an aim to identify factors that can be used to improve the detection rate of transrectal ultrasound (TRUS) biopsy of the prostate. METHODS: Between February 2000 and April 2001, 222 patients with a mean age of 64 years (range 38-85) underwent TRUS-guided 10-core prostate biopsy for either abnormal prostate specific antigen (PSA) levels (>4 ng/mL) and/or abnormal digital rectal examination (DRE). Of this number, 165 patients underwent their first biopsy, whereas 45 and 12 patients had had one or two previous biopsies, respectively. RESULTS: Prostate cancer detection rates for the initial biopsy group (n = 165), second biopsy group (n = 45) and third biopsy group (n = 12) were 29.7, 23.0 and 41.7%, respectively. Six patients who had a negative first 10-core biopsy underwent a second 10-core biopsy and one patient (16%) was found to have cancer. Apart from total prostate volume, there were no significant statistical differences between the patient age, mean total PSA, PSA density, PSA-transition zone density, DRE and TRUS findings between the initial and repeat biopsy groups of subjects who had cancer. Those who had cancer detected only on repeat biopsies had larger prostate glands (P = 0.041). CONCLUSION: Patients who had cancer detected only on repeat biopsies had bigger prostate glands, supporting the hypothesis that TRUS sextant biopsy as a technique suffers the error of under-sampling in a bigger prostate.     

The fixed flexed and subluxed knee in the haemophilic child: what should be done?

Summary. Knee haemarthroses are very common in the haemophiliac and often, despite infusion of the missing coagulation factor, synovitis develops. The warm swollen joint is maintained in the most comfortable position for the haemophiliac: flexion. Ambulation is achieved by planterflexion of the ankle joint and toewalking. As the chronic synovitis persists, the range of movement of the knee is affected, with loss of full extension. Development of radiological degenerative signs develop. The quadriceps muscle usually weaken due to disuse, but the hamstrings are active in maintaining the flexion of the joint. As the process continues, the tibia subluxes posteriorly on the condyles of the femur. The posterior capsule of the knee joint soon contracts, permanently limiting knee extension. A case is described on whom an Ilizarov device was used to gradually return the limb to a function position. This will allow the patient to complete his growth prior to a definitive orthopaedic procedure.     

Giant Asian honeybee or Bambara stings causing myocardial infarction,bowel gangrene and fatal anaphylaxis in Sri Lanka: a case series

The sting of Giant Asian honeybee (Apis dorsata) or Bambara in Sinhala and Karunge Kulavi in Tamil is a common environmental hazard in Sri Lanka known to cause immediate allergic reactions, which could be fatal in sensitized individuals. We reported myocardial infarction, bowel gangrene and fatal anaphylaxis in a prospectively proven case series and the association of these uncommon complications with delayed removal of stingers from the patients' skin.     

Empathy as a communication strategy in the pharmacy — a study based on cognitive and behavioural analysis

Objective — To evaluate an educational intervention that aimed to improve the level of empathy shown by pharmacy staff to their customers. Method — Open study of the effect of the intervention on pharmacy staff attitudes and behaviour related to empathy. All members of staff in five pharmacies in and around Stockholm, Sweden, participated in a 20‐hour continuing education course on communication and empathy. Participants worked in groups of between four and eight. Course outcomes were measured by questionnaires (to examine cognitive changes) and video‐recordings (to examine behavioural changes). Staff (n=75) completed questionnaires before and after the course. Questionnaires used Davis's empathy scale and Rosenberg's self‐esteem scale. Interactions between staff and customer were video‐recorded before and after the training course in one pharmacy. Videotapes were subsequently coded by two researchers for specific behaviours that demonstrated empathic communication. Results — The findings from both the questionnaires and the video‐recordings indicated that after the course there were small increases both in the pharmacy staff's capacity to show empathy and in some aspects of the empathic behaviour they displayed. Conclusion — Rather modest changes in empathy were found to result from the intervention and possible reasons for this are explored in the paper.