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.     

The Usefulness of Magnetic Resonance Imaging in the Diagnosis of Anterolateral Impingement of the Ankle

The purpose of this study is to assess the sensitivity and specificity of magnetic resonance imaging (MRI) in the diagnosis of anterolateral impingement of the ankle and to assess the most helpful sequence in making the diagnosis. Twenty-four patients who had undergone ankle arthroscopy were chosen. Twelve patients had arthroscopically documented anterolateral impingement, and 12 patients with no impingement on arthroscopy served as controls. Two musculoskeletal radiologists and an orthopedic surgeon, blinded to the operative diagnosis, retrospectively reviewed selective MRI images in the sagittal, axial, and coronal planes. The sensitivities and specificities were calculated for all 3 reviewers. The Kendall coefficient of concordance was calculated for overall agreement among reviewers. Sensitivities varied from 0.75 to 0.83, whereas specificities varied from 0.75 to 1.00. Using the Fisher exact test of contingency, the sensitivities and specificities showed that all reviewers' interpretations were statistically significant with P = .039, .001, and .012, respectively. The axial images were felt to be most helpful in making the diagnosis. The physicians felt that the sagittal images were helpful in 67%, 83%, and 100%, respectively. MRI is a useful tool that can aid the clinician in the diagnosis of anterolateral impingement of the ankle. T1 sagittal images demonstrating displacement of the normal fat signal anterior to the fibula by scar can be useful and help to confirm the diagnosis.     

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.     

142Effects of Low‐Frequency Ultrasound Applied In Vitro to Highly Antibiotic‐Resistant Acinetobacter Isolates Recovered From Soldiers Returning From Iraq

Abstract  Brooke Army Medical Center isolated 25 highly antibiotic‐resistant Acinetobacter ssp . (primarily A. baumannii ) from wounded soldiers returning from Iraq. Concern about effective treatment of these organisms led our institution to begin investigating low‐frequency ultrasound (LFU) as a method of increasing the effectiveness of antibiotics on A.baumannii in wound management. Studies have suggested that LFU applied in conjunction with antibiotics may increase their overall effectiveness. We hypothesize that combining antibiotics with LFU may be an effective method of wound management and that this combination may be synergistic in its overall effect. In this initial work, we wanted to determine if sonocation would have an effect on our organism of interest, A. baumannii . We selected several organisms, both gram positive and gram negative, that have been shown to be killed by sonocation ( E. coli, S. aureus , and S. pyogenes ) and added three highly resistant A. baumannii isolates. Bacterial death was measured by both colony counts after 24 hours of growth and acridine orange staining using a standard protocol.
Colony counts were significantly reduced by sonocation. Furthermore, A.'baumannii colony counts were also greatly reduced by sonocation. Actual cell destruction was also visualized using acridine orange staining. Our data support the assertion that sonocation has an antibacterial effect on some bacteria, including A. baumannii . Our next step is to add antimicrobial agents and determine if their effectiveness can be increased by sonocation.     

Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo

Background Associations between allergen challenge-induced sites of epithelial damage and the distribution of leucocytes and extravasated plasma remain unexplored. Objective To study neutrophils, eosinophils, and fibrinogen at allergen challenge-induced patchy epithelial damage-restitution sites in guinea-pig trachea. Methods After local challenge tracheal tissue (cryo sections and whole-mounts) and lumen (selective tracheal lavage) were examined at 1, 5, and 24 h. Eosinophils, neutrophils and fibrinogen were identified by histochemistry. Results Neutrophils increased markedly in tracheal lavage fluids and in tissue and were strongly associated with the challenge-induced epithelial craters of damage-restitution. At 1 and 24 h eosinophils were increased in the tracheal lumen whereas the surrounding tissue displayed a reversed pattern. Gels rich in fibrinogen, neutrophils, and eosinophils were present in epithelial crater areas, protruding into the lumen. Clusters of free eosinophil granules, Cfegs, released through lysis of eosinophils, and neutrophils with long cytoplasmatic protrusions abounded in these crater areas. Conclusions The present findings provide important new insights into allergic airways where sites of epithelial damage-restitution processes emerge as the major loci for eosinophil, neutrophil, and plasma protein activities, the latter likely causing leukocyte adhesion and activation in vivo. The disttibution of eosinophils in this study suggests roles of these cells both in airway mucosa and in regional lymph nodes. Based on the present study we also propose that lysis of eosinophils and Cfegs generation are a major paradigm for activation of these cells in vivo.     

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.     

Biochemical characterisation of para-aminophenol-induced nephrotoxic lesions in the F344 rat

The acute biochemical effects of the nephrotoxin p-aminophenol (PAP) were studied in detail using a combination of conventional bioanalytical and ¹H-NMR spectroscopic methods. Dosing PAP (25–100 mg/kg) to male F344 rats resulted in a dose-related proximal nephropathy with consequent elevations in urinary enzymes, glucose, and urine total protein as shown by conventional methodology. ¹H-NMR spectroscopy at 400 MHz of urine from PAP-treated rats also revealed a characteristic glycosuria, with concomitant amino aciduria. The increased excretion of these compounds indicates functional defects in the proximal tubule and reduced solute reabsorption efficiency. In addition, ¹H-NMR urinalysis and conventional enzymatic analysis showed a dose-related lactic aciduria. Other changes detected by ¹H-NMR included a dose-related reduction in the excretion of citrate (confirmed by a conventional biochemical method) and an increase in the excretion of acetate. The degree of abnormalities shown by ¹H-NMR urinalysis agreed well with histopathological observations and conventional biochemical indices of nephrotoxicity. ¹H-NMR urinalysis therefore serves to highlight changes in the excretion of low MW urine components not routinely studied by conventional biochemical analysis.Abbreviations ALP alkaline phosphatase - APAP paracetamol - BUN blood urea nitrogen - GFR glomerular filtration rate - GOT glutamate oxaloacetate transaminase - LAP leucine aminopeptidase - LDH lactate dehydrogenase - MW molecular weight - NAG N-acetyl--D-glucosaminidase - PAP p-aminophenol - ppm parts per million - TMAO trimethylamine N-oxide - UFR urine flow rate     

Expression microdissection: operator-independent retrieval of cells for molecular profiling.

Tissue microdissection is an important method for the study of disease states. However, it is difficult to perform high-throughput molecular analysis with current techniques. We describe here a prototype version of a novel technique (expression microdissection) that allows for the procurement of desired cells via molecular targeting. Expression microdissection (xMD) offers significant advantages over available methods, including an increase in dissection speed of several orders of magnitude. xMD may become a valuable tool for investigators studying cancer or other disease states in patient specimens and animal models.