"Alcalase" and serum proteins.
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Biomedical subjects
Publications and source records attributed to J Dolovich.
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Repeat plasma donors were studied to determine whether there was a relationship between allergic-type reactions during plasmapheresis and IgE-dependent sensitization to ethylene oxide gas used for sterilization of disposable fluid administration sets. Serums from 32 donors with allergic-type reactions and 84 donors who had no reactions but were exposed to the same materials and served as controls were tested for IgE-antibodies to ethylene oxide. The results, expressed as an IgE ethylene oxide index, were greater than 2 in 78 percent of serums from donors with allergic reactions and 12 percent of serums from controls. This association was significant (p less than 0.0001). Reactivity of the antibodies was directed against an ethylene oxide-human serum albumin conjugate and not against human serum albumin carrier protein. IgG antibodies with ethylene oxide specificity also were present in the serums of repeat plasmapheresis donors. Each of seven rabbits immunized with an ethylene oxide-protein conjugate responded with a high serum level of antibody with ethylene oxide specificity. It was concluded that the residual ethylene oxide in fluid administration sets is immunogenic and may cause allergic reactions in plasma donors.
OBJECTIVE: To compare the effect of budesonide Turbuhaler 400 microg/day with budesonide aqua 256 microg/day in the treatment of seasonal allergic rhinitis (SAR). Secondarily to ascertain patients' preferences for the two nasal devices and to assess quality of life. DESIGN: Randomized, multicentre, double-blind, double- dummy, parallel groups study. SETTING: Private practices and hospital clinics in Ontario, Quebec and Manitoba. POPULATION: Two hundred and eighty-four out-patients with SAR, who were symptomatic during the ragweed season, volunteered for enrolment (243 randomized). RESULTS: Mean daily nasal symptom scores were significantly reduced with treatment. There were no statistically significant changes from baseline for eye symptoms. Most patients (more than 80%) achieved substantial control of their symptoms with budesonide. The most common nasal and non-nasal adverse events for both groups were epistaxis and headache. Turbuhaler was easier to use and more convenient to carry, had less of an unpleasant taste, and caused less nasal irritation than the aqua spray. More than twice as many patients preferred Turbuhaler to the aqua spray (69% versus 31%). Improvement in quality of life from baseline to clinic visits was statistically significant in both groups. CONCLUSION: Once daily use of 256 mg of budesonide aqua and 400 mg of budesonide Turbuhaler are equally safe and efficacious in the treatment of SAR. Patients preferred the budesonide powder formulation delivered via Turbuhaler two to one over the aqua formulation.
BACKGROUND: Inhaled corticosteroids are effective in suppressing a chronic cough without asthma associated with sputum eosinophilia. OBJECTIVE: To investigate the inflammatory characteristics in the induced sputum of patients with a chronic cough without asthma or known cause and the effects of budesonide treatment on chronic cough in those patients. PATIENTS AND METHODS: Forty-four adults (mean [minimu, maximum] age of 45 years [20,75], 28 women, 17 atopic subjects and 32 nonsmokers], with a daily bothersome cough for at least one year and who had no evidence of asthma or other known cause for the cough, were consecutively enrolled. The trial was a randomized, double-blind, controlled parallel group trial of budesonide 400 mg twice daily for two weeks versus placebo. Patients then received open administration of the same dose of budesonide for a further two weeks. Sputum was induced before and at the end of each treatment period. Cough severity was documented by a visual analogue scale. RESULTS: Thirty-nine (89%) patients produced mucoid sputum after induction on at least one study visit. At baseline, the majority (59%) had a mild elevation in the median proportion of neutrophils (65%). All had elevated fluid phase levels of fibrinogen (3200 mg/L) and albumin (880 mg/L), and high levels of interleukin-8 and substance P. Interleukin-8 correlated with neutrophils (rho=0.72, P<0.001), fibrinogen (rho=0.65, P<0.001), albumin (rho=0.67, P=0. 001) and eosinophil cationic protein (rho=0.60, P=0.001). Substance P correlated with albumin (rho=0.60, P=0.006). No subject had an increase in eosinophils. Treatment with budesonide did not affect cough or sputum measurements. CONCLUSIONS: Patients with nonasthmatic chronic cough enrolled in this study had evidence of a mild neutrophilia and/or microvascular leakage. Chronic cough did not respond to treatment with budesonide, perhaps because the cause was not associated with sputum eosinophilia.
BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a major proinflammatory cytokine that is thought to be important in the pathogenesis of asthma. However, alterations in systemic regulation of this cytokine in asthma have not been examined in the context of corticosteroid therapy. OBJECTIVES: To examine the ability of peripheral blood mononuclear cells (PBMC) from three different groups of patients with asthma requiring varying amounts of inhaled corticosteroids (ICS) for clinical control, and to examine cells from age- and sex-matched nonasthmatic patients to produce TNF-alpha. DESIGN: All patients with asthma had a positive methacholine challenge test. 'High dose' ICS patients with asthma required ICS greater than or equal to 800 microg/day. 'Medium dose' patients with asthma were on less than or equal to 500 microg/day of ICS, whereas 'no ICS' patients with asthma had received no ICS for at least three months. Each patient with asthma was examined in parallel with an age- and sex-matched, nonasthmatic, nonatopic control subject. Cells were cultured (with or without the addition of potential stimulators phytohemagglutinin, lipopolysaccharide, formyl-methionine-leucine-phenylalanine or antihuman CD3), and TNF-alpha production was assessed by ELISA. MAIN RESULTS: PBMC from both high dose ICS (n=8) and no ICS (n=11) patients with asthma produced more than twice the amount of TNF-alpha than cells from matched nonasthmatic control patients (P<0.01) when cultured alone or in the presence of each stimulus (P<0.05). In contrast, there was no significant difference in TNF-alpha production between medium dose ICS patients with asthma and control patients. A group of asymptomatic atopic patients (n=6) did not have an increased level of TNF-alpha production. CONCLUSIONS: Increases in TNF-a production within the PBMC compartment can be observed in both patients with asthma receiving high dose ICS and in a group of patients with mild asthma receiving no ICS therapy, but not in patients with asthma receiving a medium dose of ICS or atopic patients.
Ten patients with perennial allergic rhinitis and 10 healthy subjects were studied to determine most discriminative nasal irrigation fluid marker(s) and to compare samples that were collected at baseline and over a 1-hour period, every 15 minutes. The latter were pooled and designated 1-hour sample. In the nasal irrigation we investigated the following inflammatory cells and soluble mediators: eosinophils, neutrophils, granulocyte-macrophage colony-stimulating factor, interleukin-4, interleukin-6, interleukin-8, ECP, EPX, MPO, leukotriene C4, leukotriene B4, prostaglandin E2, tryptase and fibrinogen. Patients with PAR were then treated for 2 weeks with the topical nasal steroid. The only marker that discriminated patients with perennial allergic rhinitis and healthy subjects was eosinophil count (EO%): correspondingly 14.01 +/- 5.8 and 0.18 +/- 0.09, (M +/- SD). Difference between the studied groups did not depend on the time of irrigation, baseline or 1-hour. EO% was also the only marker of a clinically successful treatment with the nasal steroid, 14.01 +/- 5.8 and 0.87 +/- 0.4, before and after treatment respectively. We conclude that EO% is the most sensitive inflammatory marker of perennial allergic rhinitis, and that baseline nasal irrigation can be used to study nasal mucosal inflammation.
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