Randomized controlled trial of unflued gas heater replacement on respiratory health of asthmatic schoolchildren

BACKGROUND: Previous studies do not provide a clear picture of the relationship between nitrogen dioxide (NO(2)) exposure and asthma. METHODS: Eighteen schools using unflued gas heating in winter were randomly allocated to either retain their heaters (10 control schools) or to have replacement flued gas or electric heaters installed at the beginning of winter (8 intervention schools). Fortnightly telephone interviews were used to record daily individual asthma symptoms that occurred over 12 weeks (including winter). Lung function and histamine challenge tests were performed at baseline and the end of the study. NO(2) was measured in each school classroom on 9 days and in each household on 3 days spread over the study period. RESULTS: From 199 primary school children that met the eligibility criteria, 45 intervention and 73 control children agreed to participate. Baseline characteristics were similar between groups. Difficulty breathing during the day (Relative Risk [RR] = 0.41; 95% CI: 0.07, 0.98) and night (RR = 0.32; 95% CI: 0.14, 0.69), chest tightness during the day (RR = 0.45; 95% CI: 0.25, 0.81), and daytime asthma attacks (RR = 0.39; 95% CI: 0.17, 0.93) were significantly reduced in the intervention group. Percentage predicted forced expiratory volume in one second (FEV(1)), the concentration of histamine inducing a 20% fall in FEV(1) (PD(20)), and the dose-response slope (DRS) were similar between groups at follow-up. Mean (standard deviation) NO(2) levels were 15.5 (6.6) parts per billion (ppb) and 47.0 (26.8) ppb in the intervention and control schools respectively (P < 0.001). CONCLUSIONS: Asthma symptoms were reduced following a replacement intervention that removed high exposure to NO(2). Such replacement should be considered a public health priority for schools using unflued gas heating during winter.     

The cardiac K+ channel KCNQ1 is essential for gastric acid secretion

BACKGROUND & AIMS: Gastric H+ secretion via the H+/K+-adenosine triphosphatase is coupled to the uptake of K+. However, the molecular identity of luminal K+ channels enabling K+ recycling in parietal cells is unknown. This study was aimed to investigate these luminal K+ channels. METHODS: Acid secretion was measured in vivo and in vitro; KCNQ1 protein localization was assessed by immunofluorescence, and acid-sensitivity of KCNQ1 by patch-clamp. RESULTS: We identified KCNQ1, which is mutated in cardiac long QT syndrome, as a K+ channel located in tubulovesicles and apical membrane of parietal cells, where it colocalized with H+/K+-adenosine triphosphatase. Blockade of KCNQ1 current by 293B led to complete inhibition of acid secretion. The putative KCNQ1 subunits, KCNE2 and KCNE3, were abundant in human stomach; KCNE1, however, was absent. Coexpression of KCNE3/KCNQ1 in COS cells led to an acid-insensitive current; KCNE2/KCNQ1 was activated by low extracellular pH. CONCLUSIONS: We identified KCNQ1 as the missing luminal K+ channel in parietal cells and characterized its crucial role in acid secretion. Because KCNE3 and KCNE2 are expressed in human stomach, one or both are candidates to coassemble with KCNQ1 in parietal cells. Thus, stomach- and subunit-specific inhibitors of KCNQ1 might offer new therapeutical perspectives for peptic ulcer disease.     

Dermal sensitization potential and inhalation toxicological evaluation of 4-phenylcyclohexene

4-Phenylcyclohexene (4-PCH) is a by-product formed in trace amounts during the production of styrene-butadiene latexes, which are used in carpet manufacturing. The dermal sensitization potential of 4-PCH was evaluated by using a modification of the Buehler method. The condition of the test site was evaluated 24 and 48 hr after the challenge application with no response observed in any of the guinea pigs. For the acute inhalation study, groups of five Fischer 344 rats/sex were exposed to 16 or 60 ppm 4-PCH for a single 6-hr exposure. Subsequently, groups of 10 Fischer 344 rats/sex were exposed to time-weighted average concentrations of 0, 1, 10, or 50 ppm (0, 6.6, 65, or 320 mg/m3) 4-PCH for 6 hr/day, 5 days/week for nine exposures. The highest vapor concentration, 50 ppm, was the maximum attainable during the course of the 2-week study. It was only achieved by acclimating the chamber with saturated vapor prior to each animal exposure. The following parameters were evaluated for the 2-week study: clinical signs, body weights, selected organ weights, hematology, clinical chemistry, urinalysis, and histopathology. All rats survived to the termination of the study and had no clinical or pathologic evidence of eye, skin, nasal, or respiratory tract irritation. There were no exposure-related effects identified in any of the parameters monitored. Thus, 4-PCH produced no toxicity at the highest concentration that could be generated and did not produce delayed contact hypersensitivity in guinea pigs.     

Molecular weight determination of the two segments of double-stranded RNA of infectious bursal disease virus,a member of the birnavirus group

The molecular weights (mol. wts.) of the two double-stranded (ds) RNA segments of infectious bursal disease virus (IBDV) were determined using previously sequenced reovirus genes M3 and S2 as internal ds RNA reference molecules. Electrophoresis under fully denaturing conditions revealed mol. wts. of 2.26 × 10⁶ daltons and 1.98 × 10⁶ daltons. By direct length measurements under the electron microscope, using two different spreading conditions, the two segments were calculated to be composed of 3274 ± 79 base pairs (bp) and 2821 ± 59 bp or 3299 ± 68 bp and 2830 ± 73 bp, resulting in mol. wts. of 2.24– 2.26 × 10⁶ daltons and 1.93–1.94 × 10⁶ daltons, respectively. Base pair distances of 2.67 ± 0.08 Å and 2.71 ± 0.11 Å in ds RNA were close to those of the A-RNA form; in ds DNA included as a control, the rise per base pair was 3.18 Å, which is consistent with published results. Mol. wts. obtained for IBDV indicate that the RNAs of the other birnaviruses are also smaller than reported.     

Erzeugung einer Allergie bei nichttuberkulösen Meerschweinchen durch tuberkelbacillenfreie Flüssigkeit

Zusammenfassung Durchspült man im Überlebendversuch tuberkulöse Meerschweinchenlungen und filtriert die Durchspülungsflüssigkeit, so kann man mit dieser gesunde Meerschweinchen allergisieren. 10 Tage nach der Erstinjektion tritt bei der Intracutanprüfung bei einem Fall bereits deutliche Kokardenreaktion auf. Die anderen Fälle zeigen bei in den nächsten Tagen wiederholten Intracutanprüfungen erst schwache, dann deutliche Kokardenreaktionen. Nach sehr kurzer Zeit (1–6 Wochen) nach der Erstinjektion verschwindet die Allergie bereits wieder.Aus der Seuchenabteilung des Instituts für Infektionskrankheiten Robert Koch [Abteilungsleiter: Prof. Dr.Schnabel].     

Respiratory health effects of nitrogen dioxide exposure and current guidelines

This article reviews (i) the role of nitrogen dioxide (NO2) in respiratory diseases, including asthma, and (ii) appraises whether current guidelines for NO2 confer an adequate margin of safety for asthmatics. Medline and Excerpta Medica (1966-1997) were searched to retrieve original epidemiological studies which examined the relationship between NO2 and respiratory diseases including asthma. Previously reported reviews of controlled clinical studies were also utilised. The results of this search were then related to current NO2 guidelines. The review of 23 outdoor and 36 indoor studies suggests that respiratory effects are associated with levels of NO2 that may be encountered in common domestic and outdoor settings. Meta-analyses of studies among the general population of children demonstrate a 20% increase in respiratory problems, including increases of asthma by 20%, and wheezing by 12% in households with gas cookers. Epidemiological evidence also indicates that hourly NO2 values of 80 ppb are likely to cause respiratory symptoms in the general population of children. Such levels are frequently present in domestic and school settings. Critical appraisal of the epidemiological evidence indicates the need for a revision of NO2 guidelines to protect both asthmatics and the general population, especially children.     

Serial sonograms to detect pancreatitis in children receiving L-asparaginase

The clinical, laboratory, and ultrasonographic findings in children receiving L-asparaginase therapy were retrospectively reviewed and correlated to determine the diagnostic reliability and clinical usefulness of serial pancreatic sonograms in detecting L-asparaginase-induced pancreatitis. A total of 217 sonograms were obtained in 92 patients. Six of the 92 (6.5%) had L-asparaginase-induced pancreatitis. The diagnosis of pancreatitis was based solely on clinical symptoms in three patients, on clinical and laboratory findings in two, and on sonographic and laboratory findings in one. No confirmed cases of pancreatitis were detected solely by ultrasonography before clinical or laboratory evidence was obtained. Sonograms were useful only in confirming clinical and/or laboratory evidence of pancreatitis, but were of no value in making the early or preclinical diagnosis of drug-induced pancreatitis. We have discontinued the practice of obtaining routine serial pancreatic sonograms in children receiving L-asparaginase at our institution.