An audit of adverse events in children sedated with chloral hydrate or propofol during imaging studies

We examined records of sedations provided by the paediatric anaesthesiology staff for 455 children (ages 1 mo-17 yr) undergoing MRI or CT scans at our institution over a twelve-month period with regard to the monitoring of adverse events: excessive sedation, agitation, vomiting, hypoxaemia, and major airway compromise. One hundred-and-thirty-one patients (29%) received chloral hydrate; 324 patients (71%) received propofol. All patients were monitored with continuous noninvasive pulse oximetry and received supplemental oxygen via nasal cannulae. Of the patients who received chloral hydrate, 64 (49%) were over one year of age; of the patients who received propofol, 318 (98%) were one year of age or older. In the chloral hydrate group, 23 patients (19%) were deemed excessively sedated and four patients (3%) were agitated; no patients in the propofol group experienced any of the adverse outcomes reviewed. Furthermore, no patients in either group had significant airway compromise and none was admitted to the hospital as a result of the sedation.     

Antihistamines Block Radiation-Induced Increased Intestinal Blood Flow in Canines

Antihistamines Block Radiation-Induced Increased IntestinalBlood Flow in Canines. COCK-ERHAM, L. G., DOYLE, T. F., DONLON,M. A., AND GOSSETT-HAGERMAN, C. J. (1985). Fundam. Appl. Toxicol.5, 597–604. Radiation-induced systemic hypotension isaccompanied by increased intestinal blood flow (IBF) and anincreased hematocrit (HCT) in dogs. Histamine infusion leadsto increased IBF and intestinal edema with consequent secretionof fluid into the intestinal lumen. This study was performedto determine whether these effects could be diminished by prioradministration of H₁ and H₂ histamine blockers. Dogs were givenan iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25mg/min) for 1 hr before and for 1 hr after radiation (H₁ andH₂ blockers, respectively). Mean systemic arterial blood pressure(MBP), IBF, and HCT were monitored for 2 hr. Systemic plasmahistamine levels were determined simultaneously. Data obtainedindicated that the H₁ and H₂ blockers, given simultaneously,were successful in blocking the increased IBF and the increasedHCT seen after 100 Gy, whole-body, radiation. However, thepostradiation hypotension was only somewhat affected, with theMBP falling to a level 28% below the preradiation level. Plasmahistamine levels reached a sharp peak, as much as 20% abovebaseline, at 4 min postradiation. These findings implicate histaminein the radiation-induced increase in IBF and HCT but not forthe gradual decrease in postradiation blood pressure     

Effect of Manganese on the Hepatic Microsomal Mixed Function Oxidase Enzyme System in the Rat

Effect of Manganese on the Hepatic Mixed Function Oxidase EnzymeSystem in the Rat , M. J., and SCHNELL, R. C. (1984). Fundam.Appl. Toxicol. 4, 1009–1018. Experiments were conductedto examine the effect of manganese on the hepatic mixed functionoxidase system in the rat Acute treatment with manganese chloride(1–10 mg Mn/kg, ip) produced a significant prolongationof hexobarbital hypnosis in male rats on Days 2 and 3 followingmetal administration. The threshold dose of manganese to producethis alteration in response was 5 mg Mn/kg and the altered responsereturned to control values by Day 5. The prolonged hexobarbitalhypnosis resulted from Mn inhibition of the hepatic microsomalmixed function oxidase system, the activity of which was assessedusing aniline (23%), ethylmorphine (26%), and hexobarbital (27%)as substrates. Manganese treatment also produced significantlyreduced levels of cytochrome P-450 (23%) and b₅ (21%), but thesubstrate-induced spectral binding of all three substrates wasnot altered significantly by Mn when expressed as A per nanomoleof cytochrome P-450. The activity of NADPH cytochrome c reductasewas also significantly decreased (25%) by Mn treatment Followingthe in vitro addition of Mn in concentrations ranging from 1x 10^–6 to 1 x 10^–3 M Mn to microsomes derived fromnaive rats, there was no decrease in the metabolism of anilineor hexobarbital or cytochrome P-450 levels. Significant inhibitionin ethylmorphine metabolism was observed with Mn concentrationsof 1 x 10^–4 m and greater. These experiments indicatethat acute Mn treatment can alter drug response as the resultof decreased hepatic biotransformation which occurs by an indirectmechanism.     

Immunosuppressive and Monooxygenase Induction Activities of Highly Chlorinated Diphenyl Ether Congeners in C57BL/6 and DBA/2 Mice

The dose-response effects of 2,2',3,3',4,5,5',6,6'–,2,2',3,3',4,4',5,6,6'-and2,2',3,3',4,4',5,5',6-nonachlorodiphenyl ether (non-aCDE) anddecachlorodiphenyl ether (decaCDE) on the splenic plaque-formingcell (PFC) response to sheep red blood cells (SRBCs) and theinduction of hepatic microsomal ethoxyresorufin O-deethylase(EROD) activity was determined in aryl hydrocarbon (Ah)-responsiveC57BL/6 and less Ah-responsive DBA/2 mice. All the congenersexhibited immunotoxicity at doses between 2.5 and 10 µmol/kgin C57BL/6 mice whereas in DBA/2 mice doses25 µmol/kgwere required to cause inhibition of the PFC response to SRBCs.The results also showed that the nonaCDE isomers and decaCDEwere more active as inducers of hepatic EROD activity in C57BL/6than DBA/2 mice; however, there was not a correlation betweenthe induced EROD activity and the CYP1A1 and CYP1A2 mRNA levelsin the C57BL/6 mice. These data suggested that the immunotoxicityof these compounds was mediated through the Ah receptor. However,the results showed that the immunotoxicity of the nonaCDE isomersand decaCDE was unexpectedly high compared to that of lowerchlorinated diphenyl ethers and there were no apparent structure-activityrelationships among the higher chlorinated congeners. This suggeststhat some of the immunosuppressive effects observed for thenonaCDE isomers and decaCDE may be Ah receptor-independent.     

Pulmonary Bioavailability and Fine Particle Enrichment of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Respirable Soil Particles

The pulmonary bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) and the enrichment of polychlorinated dioxins (PCDDs)and furans (PCDFs) in fine particles were evaluated to assessthe implications that these factors have on risk and exposureassessments. Respirable subfractions of PCDD-contaminated soilfrom a former 2,4,5-trichlorophenoxyacetic acid manufacturingsite were isolated by chemical dispersion and gravity sedimentation.Analysis of the subfractions revealed that there was a size-dependentenrichment of PCDDs and PCDFs, with smaller particles more highlycontaminated. TCDD was enriched up to 33-fold as compared tounfractionated soil. Soil and laboratory-recontaminated galliumoxide, which served as the positive control, were administeredby intratracheal instillation to female Sprague-Dawley rats.Animals were terminated up to 28 days following treatment andpulmonary bioavailability of TCDD was assessed by hepatic enzymeinduction and TCDD concentration. Enzyme induction was dependenton the duration of exposure with up to 56 and 918% increasesin cytochrome P450 and aryl hydrocarbon hydroxylase (AHH) activity,respectively, following exposure to PCDD-contaminated soil.There was no significant difference in AHH induction betweenanimals which received contaminated soil and those treated withthe positive control. Hepatic concentration of TCDD in soil-exposedrats was 115, 101, and 179% of positive controls at 1, 7, and28 days post-treatment, suggesting that the soil or co-contaminantsinfluenced retention of TCDD in the liver. These data indicatethat the relative pulmonary bioavailability of TCDD on respirablesoil particles is 100% as compared to laboratory-recontaminatedgallium oxide and that PCDDs and PCDFs are highly enriched onrespirable particles. Utilization of these results will reducethe uncertainty and improve the accuracy of envi ronmental riskassessments of PCDDs and PCDFs.     

SERUM LIPID AND APOLIPOPROTEIN A AND B LEVELS IN FAMILIAL HYPERCHOLESTEROLEMIA

Serum lipid and apolipoprotein A (apo A) and B (apo B) levels were studied in a family with familial hypercholesterolemia (FH), which comprised two heterozygous parents, five heterozygous children, one homozygote and one normal child. Lipid levels were compared with those of age- and sex-matched normal controls. All subjects with FH had total serum cholesterol and low density lipoprotein-cholesterol (LDL-C) levels greater than the 90th percentile value for the reference range. High density lipoprotein-cholesterol (HDL-C) levels were less than the corresponding 13th percentile in heterozygous subjects. The homozygous child had grossly elevated levels of LDL-C and apo B, and very low levels of HDL-C and apo A. The most powerful discriminating variable between normal, heterozygous and homozygous family members was the LDL-C/HDL-C ratio.     

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation bur absolute success races are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safely and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8–32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO ≤8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.