Serum IgE and eosinophil count in allergic rhinitis--analysis using a modified Bayes' theorem.

BACKGROUND: To use probability theory to establish threshold values for total serum IgE and eosinophil counts that support a diagnosis of allergic rhinitis and to compare our results with previously published data. METHODS: Prospective study of rhinitis patients using a modified version of Bayes' theorem. Study included 125 patients at the West Los Angeles VA Medical Center diagnosed with rhinitis who completed allergy consultation and immediate hypersensitivity skin testing. RESULTS: Eighty-nine of 125 patients were atopic by prick and/or intradermal skin testing. Using a modified version of Bayes' theorem and positive and negative probability weights, calculations for different thresholds of serum IgE and eosinophil counts were summated and a posttest probability for atopy was calculated. Calculated posttest probabilities varied according to the threshold used to determine a positive or negative test; however, IgE thresholds greater than 140IU/ml and eosinophil counts greater that 80cells/ml were found to have a high probability of predicting atopy in patients with rhinitis. Moreover, IgE had a greater influence than eosinophil count in determining posttest probability of allergy in this population. Considerable differences were noted in the IgE levels of atopic and non-atopic patients, including those with asthma or a history of smoking. However, these differences were not observed with eosinophil levels. CONCLUSIONS: Using a modified version of Bayes' theorem to determine posttest probability, IgE threshold levels greater than 140IU/ml and eosinophil counts greater than 80cells/ml in an individual with clinical signs and symptoms of rhinitis are likely to correlate with an atopic aetiology. This model of probability may be helpful in evaluating individuals for diagnostic skin testing and certain types of allergy-modifying treatment.

Interleukin-10 regulation in normal subjects and patients with asthma.

Interleukin-10 or cytokine synthesis inhibitory factor has important antiinflammatory activities in immune diseases. We speculated that diminished IL-10 production in asthma would permit the unopposed synthesis of proinflammatory cytokines, contributing to the development and severity of asthma. Our data demonstrate constitutive secretion of IL-10 into bronchoalveolar lavage (BAL) fluid of normal, nonasthmatic subjects (130 +/- 61 pg/ml; n = 8). Asthmatic patients' BAL fluid was characterized by diminished concentrations of IL-10 (9 +/- 18 pg/ml; n = 8; p < 0.01 compared with that of normal subjects). By using the RNA-based polymerase chain reaction, we demonstrated that diminished IL-10 occurred as a result of inhibition of transcription. IL-10 transcription, but not protein, was observed at the time of the late asthmatic response. We speculate that the subsequent appearance of IL-10 protein could contribute to the resolution of the late asthmatic response. Similar to what was observed in the BAL fluid, peripheral blood mononuclear cells of patients with asthma demonstrated decreased spontaneous (0.01 +/- 0.01 ng/ml-asthmatic and 0.09 +/- 0.04 ng/ml-normal; p < 0.05) and stimulated (0.60 +/- 0.22 ng/ml-asthmatic and 1.69 +/- 0.49 ng/ml-normal; p < 0.05) IL-10 production compared with normal subjects. In support of the hypothesis that IL-10 mitigates the development of inflammation, we demonstrated that the addition of a neutralizing anti-IL-10 antibody to resting peripheral blood mononuclear cell cultures of normal subjects stimulated the spontaneous production of interferon-gamma (10.4 +/- 4.3 to 152.4 +/- 23.6 ng/ml; p < 0.01). Finally, we reasoned that corticosteroids might exert at least part of their antiinflammatory activity through the induction of IL-10 secretion. However, methylprednisolone inhibited the lipopolysaccharide-stimulated production of IL-10 (2.34 +/- 0.49 ng/ml IL-10 with lipopolysaccharide alone to 1.11 +/- 0.38 ng/ml in the additional presence of 10(-6) mol/L methylprednisolone; p < 0.05).

Resolution of chronic urticaria in patients with thyroid autoimmunity.

BACKGROUND: Autoimmune disease has been implicated as a cause of chronic urticaria, and anti-thyroid antibodies have been found in patients with chronic urticaria. Because some patients with chronic urticaria and autoimmune hypothyroidism have had clinical resolution with thyroid hormone replacement, we investigated the effect of thyroid hormone in euthyroid patients with chronic urticaria and thyroid autoimmunity. METHODS: Ten euthyroid patients with refractory hives were treated with thyroxine. Seven patients had elevated anti-thyroid antibodies at baseline. Thyroid function and anti-microsomal and anti-thyroglobulin antibody levels were monitored during treatment. If a clinical response was achieved, thyroxine was discontinued and restarted if symptoms recurred. RESULTS: Seven patients with elevated anti-thyroid antibodies reported resolution of symptoms within 4 weeks. Three patients without elevated anti-thyroid antibodies did not respond. Five patients had a recurrence of symptoms after treatment was stopped, which resolved after treatment was restarted. Thyroid-stimulating hormone levels decreased in all patients with a clinical response. No correlation between clinical resolution and anti-thyroid antibody levels was seen. CONCLUSION: Thyroid autoimmunity in euthyroid patients may be associated with chronic urticaria, and treatment with thyroid suppression can result in clinical remission.

The circadian rhythm of the N-terminus and C-terminus of the atrial natriuretic factor prohormone.

Circadian variation in the circulating concentrations of the N-terminal and C-terminal portions of the atrial natriuretic factor prohormone (pro ANF) was evaluated in 8 men, ages 41-47, who have been followed for 19 years with respect to circadian variation in physiological variables including blood pressure and clinical chemistries. The N-terminus of the ANF prohormone contains two peptides consisting of amino acids 1-30 and 31-67 while the C-terminus contains 1 peptide (amino acids 99-126) of this 126 amino acid prohormone which lower blood pressure and have natriuretic properties. To determine if either the N-terminus and/or the C-terminus of the prohormone have a circadian variation in their circulating plasma concentrations these 8 men had blood samples obtained for radiommunoassay every 3 hr during a 24-hr period. Three radiommunoassays which immunologically recognize (1) the whole N-terminus (i.e. amino acids 1-98), (2) the midportion of the N-terminus (amino acids 31-67) and (3) the C-terminus (amino acids 99-126) of the ANF prohormone were utilized. The whole N-terminus, the midportion of the N-terminus which circulates after being proteolytically cleaved from the rest of the N-terminus, and the C-terminus each had a peak circulating concentration between 0400 and 0700 which were significantly (P less than 0.001) higher than their concentrations at any other time throughout the 24-hr period.(ABSTRACT TRUNCATED AT 250 WORDS)

DNase I-resistant nontranscribed spacer segments of mouse ribosomal DNA contain poly(dG-dT).poly(dA-dC).

The nontranscribed spacer regions (NTS) that adjoin the coding portion of mouse ribosomal DNA are protected in nucleoli against exhaustive DNase I digestion. Since these sequences are degraded by the enzyme after they are extracted by phenol, the protection is suggested to result from the binding of specific proteins. The nucleolar structure would thus be organized to protect NTS sequences and expose the coding sequences for transcription. We show here that these protected sequences include tracts of poly(dG-dT).poly(dA-dC). We also report that these sequences are localized in regions flanking the rRNA transcription unit. These sequences can potentially form Z-DNA. The organized DNase I-resistant NTS structure in which they participate could be involved in structuring the nucleolus or in regulating transcription because poly(dG-dT).poly(dA-dC) sequences and portions of spacer rDNA can serve as transcriptional enhancer elements.