The economic impact and medical complication rate of the common cold are well documented, but many of the physiological, inflammatory, and immune responses to common cold viruses have only recently been investigated. The purpose of this study was to compare selected systemic immune and inflammatory responses to experimental rhinovirus (RV)-39 challenge in seronegative allergic rhinitis and non-allergic rhinitis subjects. Peripheral blood was obtained before (baseline), during (acute), and 23 days after (convalescent) RV-39 intranasal challenge and assayed for leucocyte histamine release, serum immunoglobulins, allergen-specific IgE antibodies, plasma histamine, and platelet aggregation. All subjects were infected, as manifested by viral shedding in nasal secretions or seroconversion. RV-39 infection induced significant acute increases in serum IgE, leucocyte histamine release, and platelet aggregation, but caused no changes in serum IgG, serum IgA, serum IgM, and plasma histamine. The first change was confined to the allergic rhinitis subjects. There was no evidence that the acute rise in total serum IgE was due to an elevation of a pre-existing, pollen-specific serum IgE antibody. The results show that intranasal challenge with RV-39 induced changes in systemic immune and inflammatory parameters with a unique response pattern in allergic rhinitis subjects.
\s=b\Otitis media with effusion (OME) is a common middle ear inflammatory disease in the pediatric population. This article determines concentrations of three functionally and metabolically distinct inflammatory mediators in middle ear effusions (MEE) and corresponding plasma of children with OME. One hundred two patients (mean age, 4.9 years) with persistent OME were studied. Middle ear effusions were collected from all subjects and plasma from a subset at the time of tympanostomy tube insertion. Histamine was assayed radioisotopically, 13, 14-dihydro-15-keto-prostaglandin F2\g=a\(stable PGF2\g=a\ metabolite) by radioimmunoassay, and neutrophil chemotactic factor of anaphylaxis by modified Boyden chamber. Mean MEE levels of the mediators (39 \m=+-\ 13 ng/mL, 462 \m=+-\179 pg/mL, and 264% \ m=+-\ 57% positive control, respectively) were markedly higher than those of corresponding plasma (0.5 \m=+-\ 0.1 ng/mL, 285 \m=+-\127 pg/mL, and 47% \m=+-\5% positive control, respectively). The mean histamine content of mucoid effusions (43.2 \ m=+-\56.9 ng/mL) was significantly higher than that of purulent (22.5 \m=+-\10.5 ng/mL) and serous (17.9 \m=+-\ 16.8 ng/mL) effusions. Higher histamine levels were observed in effusions positive for Haemophilus influenzae when compared with those with other pathogenic isolates. The high concentrations of these mediators in MEE and their potential for inducing or sustaining the inflammatory process supports a role in the pathogenesis of OME. (Arch Otolaryngol Head Neck Surg 1988;114:1131-1133 Otitis media with effusion (OME) is a middle ear inflammatory dis¬ ease that is common in the pediatrie population. A variety of potent inflammatory mediators has been detected in middle ear effusions (MEE) of children with OME.1 More¬ over, a role for these mediators in the pathogenesis and maintenance of the disease condition was emphasized by the results of a number of recent experimental studies using animal models.2 In humans, IgE-dependent mediator release or allergy has also been incriminated as a risk factor in OME. This investigation determined MEE concentrations of two mast cellderived mediators, histamine and neutrophil chemotactic factor of anaphylaxis (NCF-A), and a stable metabolite of prostaglandin (PG)F2o. The latter two have not been previous¬ ly studied in OME. PATIENTS AND METHODSOne hundred two patients, aged 1 to 23 years (mean age, 4.9 years) with docu¬ mented persistent OME unresponsive to antimicrobial therapy were enrolled after obtaining informed consent. All patients had tympanostomy tubes inserted at which time MEEs were collected. Unilateral effu¬ sions were collected from 25 patients and bilateral effusions were collected from the remaining 17 patients. These samples were classified visually as serous, mucoid, or purulent; cultured immediately for aerobic bacteria; and a subset was submitted for complete cell count by Coulter Counter and differential. The remaining fluid (50 to 200
Protracted exposure t o high oxygen tensions has been associated in preterm neonates with egress of leukocytes and alveol a r macrophages into pulmonary interstitium and effluent obtained by bronchoalveolar lavage. Pullllonary effluent serine elastase concentrations are increased in infants 5 osed t o F.0 >.4Serum indomethacin concentrations of 10 "to 10-7 mdlh have been associated with closure of the patent ductus arteriosus. W e hypothesized that indomethacin, a potent anti -inflammatory agent, might a l t e r leukocyte chemotaxis in infants. Using modified Boyden chambers human term cord blood PMN leukocyte chemotaxis was altered (F=6.68,p=0.025) with linear attenuation ( r = -0.77) t o zymogen activated human serum. W e specul a t e that indomethacin treatment of neonates may reduce oxygen induced inflammation through reducing leukocyte induced cytotoxic parenchymal lung damage and airways inflammation in addition to closing the patent ductus arteriosus. W e describe the phenotypic and functional characteristics of an LBL derived from the bone marrow of a patient who died with an Epstein-Barr virus (EBV) related lymphoreticular malignancy 4 months a f t e r bone marrow transplantation for SCID. This LBL, designated DV-1, arose spontaneously 2-3 weeks a f t e r explantation and while i n i t i a l l y dependent on autologous fibroblasts, subsequently has been maintained in standard suspension cultures. The B-cell origin i s suggested by the absence of T-cell markers and the presence of DR and 61 antigen on 80-90%, surface IgM on 20-30%, and IgD on 20-30% of the c e l l s . The predominant light chain type i s K (72%) with a small percentage of c e l l s expressing A . The c e l l s show a normal 46XY karyotype and the host's HLA phenotype. Greater than 90% of the c e l l s are positive for EBV nuclear antigen and show the typical appearance and growth characteristics of EBV transformed LBL. Phytohemagglutinin inhibited (12-39%), pokeweed mitogen had no effect on, goat anti-u chain antiserum stimulated (57%), and staphylococcus aureus Cowan strain A inhibited (20-808) thymidine incorporation by DV-1 in a dose related manner. These characteristics are similar to those described for other EBV derived LBL's reported in the l i t e r a t u r e and to an independently derived LBL (LA350) to which we compared DV-1. This line holds useful potential for future functional and morphological studies on B-cell lines derived from immunodeficient oatients. IgA RF was p r e s e n t i n t h e s e r a o f 1 2 of 23 HSP p a t i e n t s (52%), i n c o n t r a s t t o 1 of 25 c o n t r o l s (p<0.0005). When p r e s e n t , IgA RF t i t e r s tended t o be h i g h e s t d u r i n g t h e a c u t e phase of t h e i l l n e s s . Although 64% o f HSP p a t i e n t s had i n c r e a s e d serum c o n c e n t r a t i o n s of IgA, t h e r e was no c o r r e l a t i o n between IgA c o n c e n t r a t i o n and t h e t i t e r of IgA RF (r=0.25, p>0.10). Moreover, t h e r e was no a s s o c i a t i o n between t h e p r e s e n c e o ...
A monkey model was used to evaluate intranasal ucb-28754, a newly developed H1 antagonist in attenuating nasal obstruction following intranasal challenge with either histamine or Ascaris in a dose response protocol. Nasal patency was measured with computer assisted anterior rhinomanometry. Eight female, feral, Ascaris sensitive, juvenile cynomolgus monkeys were pretreated with 100 ul of 0.075% ucb-28754 or placebo in a crossover study protocol before intranasal histamine provocation. Three of the animals also received 100 ul of 0.075% or 0.3% ucb-28754 or placebo before intranasal Ascaris challenge. Statistically significant (P < 0.05) improvement was observed for the ucb-28754 treated monkeys in nasal conductance and in mean nasal work/L following histamine challenge. Pharmacologic efficacy (50% reduction of nasal obstruction) was achieved for the medication on three of four histamine dosages. In the Ascaris challenged animals, pharmacologic efficacy was achieved for four of five doses for the animals receiving 0.075% ucb-28754 and two of five doses when they were pretreated with 0.3% ucb-28754. Measurement of heart rate, respiratory rate, and blood pressure, as well as visual examination of the monkeys indicated that ucb-28754 had no adverse effects. These studies indicate that ucb-28754 administered intranasally is a potentially safe and effective antihistamine in this monkey experimental model.
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