Oral beta2-agonist use by preschool children with asthma in East and Central Harlem, New York.

Although studies have documented underuse of controller medications and overuse of short-acting inhaled ss(2)-agonist among children with persistent asthma in disadvantaged communities, the persistence of oral ss(2)-agonist use in pediatric practice has not been studied since inhaled short-acting ss(2)-agonists became widespread. We describe medications used to treat asthma among children 3 to 5 years of age at 10 Head Start and other subsidized preschool centers in East and Central Harlem, New York City. We interviewed 149 parents/guardians of children who were identified as having probable asthma based on physician's diagnosis, persistent symptoms, hospitalization, and medication use. We classified 86 of the 149 children (58%) as having current persistent asthma. Only 15 of them (17%) were reported to have used controller medications at least 5 days/week in the last 4 weeks-only 2 of whom used inhaled corticosteroids. By contrast, 53 children (62%) used oral ss(2)-agonist in the last 4 weeks, often (72%) in conjunction with nebulized or inhaled short-acting ss(2)-agonist. Use of oral ss(2)-agonist was associated with more severe symptoms. This study documents the continued widespread use of oral ss(2)-agonist for treatment of children in a low-income community with high prevalence of asthma.     

Endotracheal diazepam: absorption and pulmonary pathologic effects

We conducted a study to evaluate the absorption of endotracheally administered diazepam and the pulmonary pathologic changes induced by its administration. Six cats received diazepam and five cats received saline endotracheally. Serial blood gases and serum diazepam levels were drawn at intervals for 90 minutes after the administration of diazepam. The cats were sacrificed after two days and their lungs were examined by a pathologist. Mean diazepam levels reached a peak two minutes after the administration of diazepam and remained elevated above therapeutic levels for 90 minutes. There was no significant change in pH, PO2, or PCO2 for either group. Histologic examination of the lungs showed a significantly increased incidence of pneumonitis in the diazepam group as compared to the saline group. This study demonstrates that although diazepam is well absorbed when administered endotracheally, it has adverse effects on the lungs that may preclude endotracheal use in the currently available commercial form.     

Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.     

Allergy to laboratory animals: a follow up study of its incidence and of the influence of atopy and pre-existing sensitisation on its development.

OBJECTIVES--To investigate the incidence of allergy to laboratory animals (ALA) during the first two years of employment, and to study the effect on ALA of atopy and sensitisation. METHODS--A follow up prospective study of ALA at the Zeneca (formerly ICI) Research Laboratories. RESULTS--The incidence of the disease during the first year of employment has remained at about 10% since the mid-1980s. This compares with an incidence of 37% in the early 1980s. The reduction in incidence and its maintenance at a lower level is thought to be due to the introduction and management of improved engineering controls, working practices, and educational programmes designed to reduce exposure to allergens from laboratory animals. The underlying incidence of immunological sensitisation to animals (the presence of immunoglobulin E (IgE) antibodies to animal allergens) is much higher (40% after one and 53% after two years of exposure). Both atopic diathesis and presensitisation to laboratory animals increased the likelihood that a person would develop ALA. CONCLUSION--Neither factor predicted the disease accurately so their use should be restricted to the identification of people who may be more susceptible to the development of ALA (and thus who may need to pay particular attention to the use of personal protective equipment) rather than to their exclusion.     

Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells

A family of five cholinergic muscarinic receptor genes (m1, m2, m3, m4, and m5) has recently been identified and cloned. In order to investigate the pharmacological properties of the individual muscarinic receptors, we have transfected each of these genes into Chinese hamster ovary cells (CHO-K1) and have established stable cell lines expressing each receptor. In the present study we have examined the antagonist binding properties of each muscarinic receptor. Antagonists were chosen that had previously been proposed to be selective for muscarinic receptor subtypes and included pirenzepine, AF-DX 116, methoctramine, dicyclomine, hexohydrodifenidol, hexahydrosiladifenidol, hexocyclium, and silahexocyclium. m1, m2, and m3 receptors express binding properties similar to those expected of high affinity pirenzepine-type receptors of cerebral cortex ("M1"), low affinity pirenzepine-type receptors of atria ("M2 cardiac type"), and the intermediate affinity pirenzepine-type receptors found in exocrine glands ("M2 glandular type"), respectively. The M1/M2 schema cannot readily accommodate the binding properties of the m4 and m5 receptors. Pirenzepine, methoctramine, and hexahydrosiladifenidol were the most selective agents for the m1, m2, and m3 receptors, respectively. None of the antagonists used in this study were uniquely selective for either the m4 or m5 receptors. The diverse binding profiles of individual cloned receptors and the widespread distribution of m1-m4 mRNAs indicate that radioligand binding studies performed on primary tissues may actually be assessing the composite properties of a heterogeneous mixture of muscarinic receptor subtypes.