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Biomedical subjects

U Pipkorn

Publications and source records attributed to U Pipkorn.

At least 37 records · Page 2Linked to original sources
PubMed1991

Allergen-induced changes in nasal secretory responsiveness and eosinophil granulocytes.

The release of toxic granule proteins from the eosinophil granulocytes is generally believed to play a crucial part in the development of allergen-induced lesions of the barrier function leading to such clinical features of continuous allergic airway disease as oedema, hypersecretion, changes in responsiveness to specific and non-specific stimuli and, in the case of the lower airways, bronchoconstriction. In the upper airways, a nasal challenge/rechallenge model has proved useful in the study of the allergic inflammatory response in hay fever patients both in experimental settings and during natural pollen exposure. Repeated nasal lavage procedures and challenges with methacholine following an initial challenge with different doses of allergen or placebo were performed in 16 hay fever patients. Following an immediate allergic reaction, a statistically significant increase in the secretory response to methacholine was seen 30 min after challenge with the higher doses of allergen (p less than 0.01) but not after the lowest dose or placebo. An influx of eosinophil granulocytes was seen within 30-60 min of the allergen challenge regardless of the dose (p less than 0.01). The activation of these cells was measured by the increased levels of ECP (eosinophil cationic protein) in the nasal lavage fluid. No relationship was found between individual changes in eosinophils or levels of ECP and changes in the secretory response to methacholine or nasal symptoms. This lends further support to our previous observations that eosinophil granulocytes are not necessarily linked to allergen-induced changes in nasal secretory responsiveness.

Adult↗
PubMed1991

Macrophages on the nasal mucosal surface in provoked and naturally occurring allergic rhinitis.

Macrophages are the most common cell type residing in the lumen of the lower airways. However, very little is known about the presence and putative pathogenic implications of macrophages in the upper airways. Using specific immunohistochemical techniques, the presence of and changes in macrophage density were studied before and after allergen exposure in the laboratory and during natural allergen exposure of subjects with seasonal allergic rhinitis. The monoclonal antibody EBM 11 combined with the alkaline phosphatase-anti-alkaline phosphatase-technique was applied on cytospin-prepared slides. In the challenge experiment, 0.5 +/- 0.2% (mean +/- SEM; n = 10) of the total cell number were positive for the EBM 11 marker before challenge, thereby not differing from the controls (0.2 +/- 0.2%; mean +/- SEM; n = 3). Local allergen challenge induced an increase of these cells to a peak of 1.3 +/- 0.4% after 4 h (p less than 0.05). During seasonal exposure there was also a similar increase, from 0.7 +/- 0.2 to 1.3 +/- 0.3% (p less than 0.05; n = 11) in placebo-treated patients and from 0.7 +/- 0.2 to 1.6 +/- 0.4% (p less than 0.05; n = 11) in patients treated with topical glucocorticoids. There was, however, no direct relationship between nasal symptoms and number of macrophages present on the mucosal surface. The study indicates that macrophages are involved in the inflammatory processes of allergic rhinitis.

Adolescent↗
PubMed1990

Vascular effects of topically applied bradykinin on the human nasal mucosa.

To evaluate the vascular effects of topically applied bradykinin on the human nasal mucosa, 13 asymptomatic hay fever patients and 11 non-allergic subjects were challenged with diluent or bradykinin in three increasing doses. Mucosal blood flow was determined with the 133Xenon wash-out method and expiratory peak flow measurements used to assess nasal airway resistance before and after challenge. Nasal symptoms were recorded. Nasal secretion quantity was measured from preweighed paper handkerchiefs. Bradykinin induced a slight increase in nasal airway resistance which was similar in both allergic and non-allergic subjects. Nasal secretion was clearly increased after challenge with bradykinin compared with challenge with diluent in both allergic and non-allergic subjects. Bradykinin did not, however, induce any change in mucosal blood flow in either group. The present findings could be explained by direct effects of bradykinin on the vascular bed without reflex activity. Bradykinin would then induce an increase in vascular permeability with subsequent oedema formation and increased amounts of fluid on the mucosal surface. In contrast to allergen challenge, bradykinin challenge had no effect on the resistance vessels, changes of which had previously been shown to be largely reflex-mediated.

Administration, Topical↗
PubMed1990

Albumin, bradykinins, and eosinophil cationic protein on the nasal mucosal surface in patients with hay fever during natural allergen exposure.

This study examined plasma- and eosinophil-derived products in nasal lavage fluids obtained from patients with hay fever during natural allergen exposure. Nine patients with strictly seasonal allergic rhinitis and five normal, nonallergic subjects (control group) were studied. Nasal lavages were performed twice weekly, starting 1 week before the expected birch-pollen season and continuing for 6 weeks, thereby covering the entire birch-pollen season. Nasal symptoms and pollen counts were recorded daily. The lavage fluid was analyzed for it content of albumin, bradykinins, and eosinophil cationic protein (ECP). During the pollen season, each of these solutes was significantly increased in the nasal lavage fluid from the allergic patients (p less than 0.05) but not from the control subjects. Albumin, bradykinins, and ECP generally correlated better between themselves than with symptoms and pollen counts. We conclude that natural exposure to allergens induces plasma exudation and increased levels of ECP on the human nasal mucosa.

Adolescent↗
PubMed1990

Measurement of histamine in nasal lavage fluid: comparison of a glass fiber-based fluorometric method with two radioimmunoassays.

The determination of histamine in nasal secretions and nasal lavage fluid may be of importance to monitor activation of histamine containing cells in the nasal cavity. However, such studies have been besieged by controversy, specifically to findings of changes in histamine levels in relation to allergenic stimulation. This controversy may be due to the specificity and accuracy of the various methods used to determine histamine in the nasal fluid. We have therefore applied and compared three new methods to determine histamine in nasal lavage fluids obtained before and after allergen challenge in normal subjects and patients with allergic rhinitis. We used a fluorometric glass fiber-based histamine method (FHR) and two RIAs, I and II. The FHR (detection limit, 7.0 nmol) and the RIA II (detection limit, 0.2 nmol) are specific for histamine itself, whereas the RIA I (detection limit, 18.0 nmol) measures mainly methylhistamine and cross-reacts to some extent with histamine. The histamine levels in the nasal lavage fluids from the nasal challenges demonstrated histamine values between 100 and 2000 nmol/L of histamine with significantly higher levels in the postallergen challenges for the allergic subjects as compared to the normal control subjects. The FHR correlated well with the RIA I and RIA II methods with correlation coefficients of 0.77 to 0.88 (p less than 0.001), respectively. However, the RIA I (methylhistamine antibody) always demonstrated absolute histamine values 5% to 20% of values measured by the RIA II (at the level of cross-reactivity to histamine).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Allergen-induced increase in nonspecific nasal reactivity is blocked by antihistamines without a clear-cut relationship to eosinophil influx.

Antihistaminic compounds have been suggested to possess other properties besides H1-receptor antagonism. To evaluate whether two different antihistamines could inhibit local eosinophil infiltration and allergen-induced nonspecific nasal hyperreactivity, 15 subjects with seasonal allergic rhinitis participated in a double-blind, randomized, placebo-controlled study outside the pollen season. At steady-state levels of either 60 mg of terfenadine, twice daily, cetirizine, 10 mg once daily, or placebo, a nasal methacholine challenge was performed before and 24 hours after a nasal allergen challenge. The volume of the methacholine-induced nasal secretions was measured. The response to allergen was determined with a scoring technique. Cells from the nasal mucosal surface were harvested with the aid of a rhinobrush. Both antihistamines induced a similar (p less than 0.01) reduction in nasal symptoms after the allergen challenge compared with placebo. Both antihistamines inhibited the increased nonspecific nasal reactivity induced by methacholine 24 hours later (p less than 0.05). The allergen challenge induced an increase in surface eosinophils, which, however, appeared unaffected by any of the active treatments. Since histamine per se does not induce changes in nonspecific reactivity, we suggest that the antihistamines possess other properties besides being H1-receptor antagonists.

Allergens↗
PubMed1990

H1-antagonists as a tool in clarifying the pathophysiology of nasal allergy.

Various mediator systems have been stressed as important in the generation of the signs and symptoms of allergic disease such as hay fever. Nevertheless, in the upper airways, histamine is still the only mediator which behaves consistently in terms of release at appropriate challenge, produces all the major symptoms of rhinitis at a local challenge, and the specific antagonist influences the signs and symptoms of rhinitis in the challenge situation as well as during natural allergen exposure. Although the majority of hay fever symptoms are influenced by H1-receptors, there are exceptions. An important one is the symptom of nasal blockage, which is due to tissue oedema and a decrease in the tone of the capacitance vessels. Another point to be stressed is that histamine alone does not induce any protracted mucosal inflammatory response with associated symptoms, influx of eosinophils and increase in responsiveness that is associated with the exposure to allergen. Nevertheless, from a clinical point of view, antihistamines are still valuable pharmacological agents for the clinical management of hay fever symptoms.

Histamine H1 Antagonists↗
PubMed1990

The 'nasal pool' device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions.

A 'nasal pool' (NP) device, a compressible plastic container with an adapted nozzle, was used to perform a continuous 10-min nasal provocation and lavage. This novel technique brings known concentrations of agents into contact with a large and defined area of the nasal mucosal surface for extended periods of time. Simultaneously, the surface exudations/secretions of the same nasal mucosa are effectively sampled by the NP fluid. A concentration-response study of histamine (80, 400 and 2000 micrograms/ml) was performed in 12 normal subjects on three different occasions. Exudation of plasma albumin into the lavage fluid was measured to quantitate the histamine-induced airway inflammation. The effect of the dwell time on exudation was examined using histamine (400 micrograms/ml) instilled in the nasal cavity for time periods from 10 sec to 10 min. The time course of histamine-induced plasma exudation response was studied by exposing the mucosa to histamine (400 micrograms/ml) for 12 min, with the NP renewed every minute. Allergen-provocations were performed in subjects with hay fever and TAME-esterase activity in the returned lavage fluid was determined to indicate the degree of response. Histamine produced a concentration-dependent increase in albumin levels in the NP fluid; 123.3 +/- 25.6, 213.8 +/- 19.7 and 430.2 +/- 32.0 micrograms/ml (mean +/- s.e.m.), respectively. The time-course study demonstrated that plasma exudation into the lumen occurred promptly and that the exudation response reached a maximum after exposure to histamine for 6-10 min. The dwell-time experiments supported this finding. After 10 min the exudation appeared to decline despite the continued presence of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Changes in non-specific nasal reactivity and eosinophil influx and activation after allergen challenge.

It has been suggested that the eosinophilic granulocyte plays a crucial role in the genesis of increased reactivity of the airways. In order to characterize changes in non-specific reactivity in the upper airways following a nasal allergen challenge further 16 subjects with strictly seasonal allergic rhinitis were studied. They were challenged with allergen outside the relevant pollen season and monitored at intervals for a period of 24 hr for nasal symptoms, changes in nasal reactivity, eosinophil influx and activation, and markers of inflammation. The same challenge sequence without an initial allergen challenge was used as a control. A symptom score technique was used to record nasal symptoms and methacholine challenges were used to monitor changes in non-specific reactivity. A nasal lavage was made prior to each methacholine challenge to monitor the influx of cells, specifically eosinophils, and to determine changes in the levels of eosinophil cationic protein (ECP) and TAME-esterase activity. Cells from the mucosal surface were also collected with a Rhinobrush prior to the allergen challenge as well as at the 24-hr follow up. The allergen challenge induced a five-fold increase in non-specific nasal reactivity, as measured by the methacholine challenges, at the 2-hr follow up from 0.051 ml +/- 0.012 (mean +/- s.e.m.) to 0.255 +/- 0.062 (P less than 0.01) and a significant increase was also noted at all observation points, whereas no increases could be observed in the control setting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effect of a single dose of a topical glucocorticoid and a cyclo-oxygenase inhibitor on allergen-induced changes in nasal reactivity.

The inflammatory response of airway mucosa to allergen exposure is a complex phenomenon featuring symptoms, the influx of inflammatory cells, the release of mediators, and changes in local reactivity. These features and their pharmacological modifications can be successfully studied in nasal challenge models. We performed a nasal allergen challenge followed by a rechallenge with allergen 24 h later in order to monitor changes in specific reactivity due to the initial allergen challenge. Symptoms were monitored, as was the generation of TAME-esterase activity in nasal lavage fluids. Prior to each challenge a nasal brush specimen was taken. In a double blind, cross-over, double-dummy manner the patients were pretreated with placebo, a single dose of 200 micrograms of budesonide (topical corticosteroid) given 2 h prior to rechallenge with allergen or 600 mg ibuprofen (cyclooxygenase inhibitor) given per os t.i.d. to steady state starting 24 h prior to the initial allergen challenge. Treatment with ibuprofen induced a slightly lower composite symptom score (P less than 0.05) at the initial allergen challenge when compared with placebo. No differences were noted in the relevant TAME-esterase activities. The allergen challenge resulted in significantly increased proportions of eosinophils in the brush specimens 24 h after the initial allergen challenge (P less than 0.001) with no differences between the different treatment alternatives. At rechallenge there was a reduction in the symptoms of secretion and nasal blockage in both groups receiving active treatment compared with placebo (P less than 0.05), whereas the number of sneezes was not affected and no differences were noted in TAME-esterase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1990

Blood flow in histamine- and allergen-induced weal and flare responses, effects of an H1 antagonist, alpha-adrenoceptor agonist and a topical glucocorticoid.

Allergen has previously been shown to induce a continuous increase in local dermal blood flow after a prick test in allergic subjects, whereas histamine induced, initially, similar peak increases in blood flow of much shorter duration. Blood flow changes induced by histamine and allergen have now been evaluated (i) after pretreatment with a local corticosteroid cream, clobetasole-17-propionate; (ii) after oral administration of the H1-antihistamine loratadine; and (iii) after oral pretreatment with the alpha 1-adrenoceptor agonist pseudoephedrine. Blinded placebo-controlled designs were used in the substudies. Laser doppler flowmetry was used for non-invasive recording of changes in local blood flow intermittently for 24 h after the topical corticosteroid, 6 h for the substudies on loratadine and pseudoephedrine. The size of the immediate weal and flare reactions, as well as late phase reactions, were also determined. Pretreatment with clobetasole-17-propionate cream on the skin for 1 week prior to prick tests did not affect the blood flow response elicited by histamine or allergen, in either the initial part (up to 1 h) or the protracted 24 h determinations. The size of the weal and flare reactions decreased. Loratadine and pseudoephedrine did not reduce the initial allergen-induced increase in blood flow, while lower blood flow compared with placebo pretreatment was noted for the protracted (1-6 h) determinations. Blood flow changes after histamine were unaffected. The histamine-induced weal and flare was inhibited by loratadine more effectively than the corresponding allergen-induced reaction. The weal and flare reactions after histamine and allergen were not changed after pseudoephedrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1990

Clearance of 99mTc DTPA from guinea pig nasal, tracheobronchial, and bronchoalveolar airways.

Technetium-99m labelled diethylenetriamine penta-acetate (99mTc-DTPA) was used to compare small solute absorption (clearance) from nasal, tracheobronchial, and bronchoalveolar airways in anaesthetised guinea pigs. 99mTc DTPA dissolved in saline was superfused through nasal and orolaryngeal catheters on to nasal and tracheobronchial airways; a small particle aerosol of nebulised 99mTc DTPA was delivered to the bronchoalveolar airways through a tracheostomy. Radioactivity over the appropriate region was then determined with a gamma camera. Mucociliary transport of 99mTc DTPA appeared not to contribute to the disappearance of 99mTc DTPA. Time-activity curves were obtained and half life values calculated by fitting a monoexponential equation to the experimental data. A progressive reduction in 99mTc DTPA was recorded from the nasal and tracheobronchial airways and from the bronchoalveolar airway, suggesting that absorption was occurring. The disappearance of 99mTc DTPA was fastest from the bronchoalveolar region, which also had the largest mucosal surface. The similar shape of the retention curves for the nasal and tracheobronchial regions suggests that the characteristics of nasal absorption of 99mTc DTPA could prove applicable to the tracheobronchial region. It is proposed that the present methods are suited for comparing the pharmacology of small solute absorption across nasal, tracheobronchial, and bronchoalveolar airway mucosa.

Absorption↗
PubMed1990

Mast cells, tissue histamine and eosinophils in early- and late-phase skin reactions: effects of a single dose of prednisolone.

Skin prick tests with allergen and histamine were performed on the volar aspect of the forearms in a double-blind, cross-over study with 40 mg of prednisolone and placebo in 16 pollen-allergic subjects. Skin biopsies were taken before any treatment and 15 min (group 1; n = 8) and 6 h (group 2; n = 8) after local challenge with allergen, corresponding to the timing of an early- and late-phase reaction. The specimens were used for the histological evaluation of mast cell and eosinophil density as well as for the determination of the histamine and protein content. The size of the induced weal and flare area as well as of any late-phase reaction was determined using digitized planimetry. The single dose of prednisolone, given 2 h prior to challenge, did not affect the size of the weal and flare response. Only 4 of the individuals developed a visible late-phase response. Eosinophils were virtually absent before allergen exposure, but were already present 15 min after allergen challenge, largely associated with the blood vessels, and were numerous at 6 h. There was, however, no relationship between eosinophil density and the presence or extent of any visual late phase. The mast cells/basophils showed a tendency to increase at the 6-hour determination. The infiltration of eosinophils was blocked by the glucocorticoid. This treatment also induced a difference in the mast cell density at the 6-hour determinations, associated with a similar difference in the histamine content of the biopsy specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Glucocorticoids.

Explore the source record for details and available documents.

Administration, Topical↗
PubMed1990

IgE-positive mast cells on the human nasal mucosal surface in response to allergen exposure.

IgE-bearing mediator cells are suggested to be the effector cells in type I allergic rhinitis. These cells can be demonstrated by their granular constituents or by the surface-bound IgE antibodies. We developed immunohistochemical techniques in order to stain the cell-bound IgE using polyclonal or monoclonal anti-human IgE antibodies. These techniques can be applied to nasal biopsies as shown previously or to cytospin specimen harvested by a brush method. They deliver excellent staining results with well-preserved morphological details. Brush samples were taken from 24 grass pollen allergic subjects before season, after a nasal allergen provocation and two weeks after the onset of season. There was a statistically significant increase in toluidine blue positive and IgE-positive cells 24 hours after nasal provocation (app. 12-fold, p less than 0.05) and more pronounced within the season (app. 58-fold, p less than 0.001) compared to preseasonal values. These cells appeared to be mast cells rather than blood basophils judged by morphological criteria. There was a striking correlation between the number of toluidine blue cells and that of IgE-positive cells (r = 0.98). The number of eosinophils also increased due to the seasonal allergen exposure (p less than 0.001), but less pronouncedly compared to the mast cells. These data re-emphasize the migration of IgE-bearing mast cells and eosinophils into the epithelial lining of the nasal mucosa due to allergen interaction and point to a possible role of mast cells as a carrier for IgE-molecules.

Adult↗
PubMed1989

Leukotriene B4 as a mediator of early and late reactions to antigen in humans: the effect of systemic glucocorticoid treatment in vivo.

The role played by leukotriene B4 (LTB4) in human allergic reactions has been the subject of recent interest and speculation. To characterize further the role of this mediator, we quantitated LTB4 levels in nasal washing by radioimmunoassay in 13 atopic subjects during immediate and late reactions after nasal antigen challenge while the subjects were taking placebo or prednisone (20 mg every 8 hours for 48 hours) in a double-blind, placebo-controlled, crossover protocol and compared these levels with levels of seven nonatopic subjects undergoing similar nasal antigen challenge. Nasal antigen challenge of atopic subjects resulted in an increase in LTB4 levels during the immediate reaction in 10 of 13 subjects (9/13 with a greater than 50% increase over baseline) with no similar increase observed in nonatopic subjects (p less than 0.05). An increase in LTB4 levels was observed in 12/13 atopic subjects (6/13 with greater than 50% increase over a second baseline) during late time periods (p less than 0.05), which was associated with an influx of neutrophils (from 65,000 +/- 43,000 to 1,246,000 +/- 829,000; p less than 0.05). However, nonatopic subjects appeared to demonstrate a similar late increase in LTB4 levels. High-performance liquid chromatography analysis of immunoreactive LTB4 demonstrated that 84% of immunoreactive LTB4 coeluted with the biologically isomer during the immediate reaction, whereas 44% to 61% coeluted with the biologically active isomer during late reactions. Steroid pretreatment had no effect on either the early or late increase in LTB4 levels or on the neutrophil influx observed during the late reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Major basic protein and eosinophil-derived neurotoxin concentrations in nasal-lavage fluid after antigen challenge: effect of systemic corticosteroids and relationship to eosinophil influx.

The late-phase response to nasal challenge with antigen is associated with a mixed inflammatory cell influx in which the eosinophil demonstrates the earliest and greatest proportionate rise. We investigated the evidence for activation of the eosinophil during the late response by measuring the concentration of the eosinophil-derived mediator major basic protein (MBP) and the eosinophil-derived neurotoxin (EDN) in nasal-lavage fluids before and for 11 hours after antigen challenge in 13 subjects with seasonal allergic rhinitis. The subjects received oral prednisone (20 mg three times daily) or placebo in a double-blind, crossover manner for 2 days before each of two antigen challenges. After placebo pretreatment, significant increases over diluent baseline (4.5 +/- 0.4 ng/ml) occurred in the levels of MBP in nasal-lavage fluid during the early (9.8 +/- 2.9 ng/ml; p less than 0.005) and late (15.3 +/- 4.8 ng/ml; p less than 0.01) responses to antigen challenge. Significant increases (p less than 0.05) in the concentration of EDN also occurred during the late response to antigen that correlated with the levels of MBP (r = 0.48; p less than 0.001). The cumulative late-phase increase in MBP correlated closely (rs = 0.96; p less than 0.005) with the total influx of eosinophils. Oral prednisone pretreatment significantly reduced the mean of each subject's peak late-phase concentration of both MBP (30.7 +/- 5.8 ng/ml versus 13.3 +/- 4.3 ng/ml; p = 0.005) and EDN (885 +/- 659 ng/ml versus 71 +/- 41 ng/ml; p less than 0.05). These data provide evidence for eosinophil degranulation during the late response and inhibition of this response by prednisone, supporting its pathogenetic role.

Blood Proteins↗