Esophageal IgG4 levels correlate with histopathologic and transcriptomic features in eosinophilic esophagitis.

BACKGROUND: Recent data associate eosinophilic esophagitis (EoE) with IgG4 rather than IgE, but its significance and function have not been determined. Our aims were to measure esophageal IgG4 levels and to determine functional correlations as assessed by histologic and transcriptome analyses. METHODS: This case-control study included pediatric subjects with EoE (≥15 eosinophils/HPF) and non-EoE controls. Protein lysates were analyzed for IgA, IgM, and IgG1-IgG4 using the Luminex 100 system; IgE was quantified by ELISA. Esophageal biopsies were scored using the EoE histology scoring system. Transcripts were probed by the EoE diagnostic panel, designed to examine the expression of 96 esophageal transcripts. RESULTS: Esophageal IgG subclasses, IgA, and IgM, but not IgE, were increased in subjects with EoE relative to controls. The greatest change between groups was seen in IgG4 (4.2 mg/g protein [interquartile range: 1.0-13.1 mg/g protein] vs 0.2 mg/g protein [0.1-0.9]; P < .0001). Tissue IgG4 levels correlated with esophageal eosinophil counts (P = .0006); histologic grade (P = .0011) and stage (P = .0112) scores; and IL4, IL10, IL13, but not TGFB1, expression and had strong associations with a subset of the EoE transcriptome. Esophageal IgG4 transcript expression was increased and correlated with IgG4 protein levels and IL10 expression. CONCLUSION: These findings extend prior studies on IgG4 in adult EoE to the pediatric population and provide deeper understanding of the potential significance and regulation of IgG4, demonstrating that IgG4 is a relevant feature of the disease; is closely related to esophageal eosinophil levels, type 2 immunity and T regulatory cytokines; and is likely produced locally.

Blood lead content in a peri-urban population of the South American toad Bufo arenarum.

Blood Pb concentration in a South American toad Bufo arenarum population (n = 152) was determined over 10 samplings carried out between December 1996 and November 1999. The studied population lived in the surroundings of the La Plata City, the largest industrial-urban setting of the Buenos Aires Province, Argentina. The presence of the metal was detected in all the samples tested, the mean concentration range being 1.99-4.66 mg dl(-1). Some preliminary environmental data on soil content of Pb in the sampling area suggest the anthropogenic origin of the metal possibly due to high rate of Pb-containing gasoline utilisation until recently. The reported results may reflect a sequel of a sustained local air-soil-water pollution process.

Blood lead concentration and delta-aminolevulinic acid dehydratase activity in adult Bufo arenarum.

The effects of sublethal doses of lead (as acetate) on blood parameters of adult male Bufo arenarum were studied. Toads received one single injection with 10, 25, 50 or 100 mg/kg of body weight, equivalent to approximately 1/90-1/10 of the 120 h-LD50; seven days after the injections, the hematocrit and the blood delta-aminolevulinic acid dehydratase (ALAD) activity were measured. Hematocrit of lead-injected animals did not exhibit significant changes respective to controls that received sodium acetate (range 29.8-38.8%). Blood lead concentrations were positively and significantly correlated with the injected metal doses. Blood ALAD activity declined proportionately to the doses of the metal as well as to its whole blood concentration. Because of its sensitivity and specificity, it was concluded that the activity of delta-ALAD may be adopted as a reliable biomarker of Bufo arenarum experimental lead intoxication.

Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study.

Obstructive sleep apnea syndrome is a well recognized cause of excessive sleepiness; however, the relation of sleepiness to mild sleep-disordered breathing (SDB), which affects as much as half the adult population, is uncertain. In order to explore this relation, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study, a longitudinal study of the cardiovascular consequences of SDB. The study sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep-disordered breathing was quantified by the respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, measured during in-home polysomnography. When RDI was categorized into four groups (< 5, 5 to < 15, 15 to < 30, >/= 30), a significantly progressive increase in mean ESS score was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5 to 9.3 (4.9) in subjects with RDI >/= 30 (p < 0.001). There was no significant modification of this effect by age, sex, body mass index, or evidence of chronic restriction of sleep time or periodic limb movement disorder. The percentage of subjects with excessive sleepiness, defined as an ESS score >/= 11, increased from 21% in subjects with RDI < 5 to 35% in those with RDI >/= 30 (p < 0. 001). We conclude that SDB is associated with excess sleepiness in community-dwelling, middle-aged and older adults, not limited to those with clinically apparent sleep apnea.

Red blood cell osmotic fragility in Bufo arenarum exposed to lead.

The effects on red blood cells of a single sublethal dose of Pb of 100 mg kg-1 administrated to adult Bufo arenarum were studied. The blood d-aminolevulinic acid dehydratase (d-ALAD) activity, the red blood cell (RBC) osmotic fragility (OF), and the hematocrit (Hct) were measured in control and lead poisoned toad. The enzyme d-ALAD is considered as a specific biomarker for human and animals lead exposure. In Bufo, lead also provoked a significant decrease in the d-ALAD activity without changes in the Hct. OF test was used to compare the impact of Pb on the extent of the RBC hemolysis produced by osmotic stress. Experimental data (absorbance of solubilized hemoglobin and [NaCl]) were fitted to the Orcutt et al. equation (1995) that allows a precise characterization of the parameters involved in OF. In blood from injected toads, the OF resulted significantly reduced. These changes were interpreted as a consequence of alterations in the composition and conformation of the RBC membrane due to Pb, as it was described for human erythrocytes.

Institutionalized ambiguity. Conflict and continuity in the American hospital.

A closer look at historical attitudes toward hospitals illuminates contradictory expectations that make it difficult for the contemporary hospital to define and fulfill its role.

Disease in history: frames and framers.

In some ways disease does not exist until we agree that it does--by perceiving, naming, and responding to it. These acts of agreement have during the past century become increasingly central to social as well as medical thought. What is often overlooked, however, is the process of disease definition itself--the fashioning of explanatory "frames" for understanding disease--and the consequence of those definitions, once they are agreed upon, in the lives of individuals, in the making and discussion of social policy, and in the structuring of medical care. More study is needed of the individual experience of disease in time and place, the relation of culture to definition of disease, and the role of the state in defining and responding to disease.