Effects of inhalation exposures to an M1-receptor agonist on ventilation in rhesus monkeys.

Information was needed on effects of possible occupational inhalation exposure to an M1-receptor agonist (xanomeline) such as might occur during the manufacturing process. Both acute and repeated inhalation exposures to xanomeline were carried out in six male rhesus monkeys using a head-dome exposure system. Exposure concentrations ranged from 0.3 to 10 mg/m3. The exposure durations were up to 2 weeks. Decreases in tidal volume and increases in respiratory frequency were both time and concentration related during acute exposures. These effects were blocked with atropine pre-treatment. Correlation with pulmonary resistance measurements in two monkeys suggested that these were bronchoconstrictive changes that increased with severity with time at a given concentration and with concentration when measured after a constant exposure time. The dose-response was relatively steep with 10 mg/m3 becoming intolerable to the monkeys after approximately 15 minutes, but no measurable effects were observed at 0.3 mg/m3 after up to 4 hours of exposure. To investigate the effects of repeated exposures, monkeys were exposed for 4 hr/day, 5 days/wk for 2 weeks to 0.0 (air only), 0.3, and 1.2 mg xanomeline/m3 of air. When compared to the air-only exposure, 0.3 mg/m3 caused no significant changes in tidal volume. In contrast, 1.2 mg/m3 caused a rapid and significant decrease in tidal volume that was sustained throughout the 4-hr exposure. A slower rise in breathing frequency also occurred. Repeated exposures did not alter the effects seen after a single exposure. It is concluded that xanomeline, a M1-receptor agonist, can acutely alter normal ventilation in non-human primates at airborne concentrations > or = 0.6 mg/m3 and should be carefully controlled in a manufacturing environment. The no-observed-effect concentration was 0.3 mg/m3.     

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A predictive model to estimate the risk of serious bacterial infections in febrile infants

Low risk criteria have been defined to identify febrile infants unlikely to have serious bacterial infection (SBI). Using these criteria approximately 40% of all febrile infants can be defined as being at low risk. Of the remaining infants (60%) only 10%–20% have an SBI. No adequate criteria exist to identify these infants. All infants aged 2 weeks-1 year, presenting during a 1-year-period with rectal temperature 38.0°C to the Sophia Children's Hospital were included in a prospective study. Infants with a history of prematurity, perinatal complications, known underlying disease, antibiotic treatment or vaccination during the preceding 48 h were excluded. Clinical and laboratory variables at presentation were evaluated by a multivariate logistic regression model using SBI as the dependent variable. By using likelihood ratios a predictive model was derived, providing a post test probability of SBI for every individual patient. Of the 138 infants included in the study, 33 (24%) had SBI. Logistic regression analysis defined C-reactive protein (CRP), duration of fever, a standardized clinical impression score, a history of diarrhoea and focal signs of infection as independent predictors of SBI.Conclusion CRP, duration of fever, the standardized clinical impression score, a history of diarrhoea and focal signs of infection were the independent, most powerful predictors of SBI in febrile infants, identified by logistic regression analysis. Although the predictive model is not validated for direct clinical use, it illustrates the clinical potential of the used technique. This technique offers the advantage to assess the probability of SBI in every individual infant. This probability will form the best basis for well-founded decisions in the management of the individual febrile infant.     

General health damage by restorations of composite

It seems warranted to state that the fourth generation bonding systems have diminished the probability of bacterial damage to the dental pulp. Dentin and in particular the bonding system may protect the pulp partly at least against toxic side-effects of the numerous components leaching from the composite and against the temperature rise caused by the setting reaction. Generalized toxic side-effects caused by the substances released by the restoration and its bonding system are not impossible and are suspected because of in vitro research, but they are assessed to be unlikely in vivo. Generalized and local allergic reactions may appear. The prevalence of allergy to composite may be higher than due to dental silver amalgam, lichenoid lesions excepted. Yet, allergic reactions are not often reported, supposedly because it is either not observed or possibly due to a lack in awareness of such symptoms.     

Intravenous sedation with propofol in dental treatment. Experience in mentally handicapped patients

Simple dental procedures in mentally handicapped patients can be facilitated by the use of intravenous sedation. This article describes our experiences with eleven such patients undergoing a total of eighteen procedures in 1994-1995. Sedation was administered by a consultant anesthetist using propofol in 'Sterrenberg'--a home for the mentally handicapped in the Netherlands. The article describes the organization of the patients selection and pre- per- and post-sedation care using a management protocol. It is concluded that the technique is effective and safe for simple dental procedures such as examination, removal of tartar, radiography and the treatment of cavities, provided that patients selection and care are meticulous.