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Biomedical subjects

U Pipkorn

Publications and source records attributed to U Pipkorn.

At least 73 records · Page 4Linked to original sources
PubMed1988

Topical glucocorticosteroids and allergen-induced increase in nasal reactivity: relationship between treatment time and inhibitory effect.

The effect of topical glucocorticosteroids on the allergen-induced nasal hyperresponsiveness, with special reference to treatment time, was studied in a double-blind, randomized, placebo-controlled crossover study. Ten patients who previously had shown allergen-induced nasal hyperresponsiveness participated. After pretreatment with either placebo or various periods with topical glucocorticosteroids, they were subjected to an initial challenge with three increasing doses of allergen and were rechallenged after 24 hours with the lowest allergen dose from the previous day. The nasal responses were monitored by means of symptom scores and measurements of N alpha-p-tosyl-L-arginine methyl esterase (TAME) activity in nasal lavages. Five different treatment schedules were used. In the active treatment alternatives, the glucocorticosteroid treatment was started 48, 12 or 2 hours before or 2 hours after the initial allergen challenge. All treatments were continued up to rechallenge on the second day. As the active treatment we used budesonide, 100 micrograms in each nasal cavity every 12 hours. After placebo pretreatment, as expected, there was an increase in nasal symptoms at rechallenge as compared with the initial allergen challenge with the same allergen dose. The mean (+/- SEM) number of sneezes increased from 5.1 +/- 1.7 to 9.5 +/- 2.0 (p less than 0.05), a composite nasal symptoms score increased from 3.3 +/- 0.66 to 4.4 +/- 0.7 (NS), and TAME activity increased from 14.9 +/- 2.83 to 25.3 +/- 0.5 cpm.10(3) (p less than 0.05). Topical glucocorticosteroid treatment abolished this increase in nasal symptoms and TAME activity (p less than 0.05 for all treatment alternatives).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1988

The cellular response of the human allergic mucosa to natural allergen exposure.

It has been suggested that the IgE-dependent late-phase reaction to allergen exposure, with the features of an inflammatory cellular infiltration and airway hyperreactivity, is a link between anaphylaxis and continuous allergic airway disease. Our main knowledge of the cellular response to allergen in sensitized individuals has been derived from allergen-challenge models. To explore the dynamics of the cellular response during the actual disease, patients with a strictly seasonal allergic rhinitis were studied during natural allergen exposure. Ten patients suffering from an isolated birch-pollen allergy were followed from a symptom-free state before, during, and to the height of the birch-pollen season. Repeated parallel cell samplings from the nasal mucosa were performed with cytologic imprints on plastic strips, nasal lavages with the recovery of the cells in the lavage fluid with cytocentrifugation on object slides for cytologic study, and scrapings from the nasal surface with a curette for histologic and ultrastructural evaluation. The histamine content was determined in lavage fluid and cell pellets. The tosyl-alpha-tosyl-L-arginine methyl esterase activity of the nasal lavage fluid was also determined as a biochemical marker of the allergic inflammatory reaction. The birch-pollen season was moderate in terms of pollen counts, and this resulted in mild to moderate nasal symptoms that ran parallel to the birch-pollen counts. The total number of cells recovered in the lavage fluid was 1.2 +/- 0.4 (SEM) x 10(6) before and 3.2 +/- 2.0 per 10(6) cells (not significant) during pollen exposure. Most cells were neutrophils and mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Studies on the allergic and nonallergic nasal inflammation.

Nasal lavage after antigenic and nonantigenic nasal stimulation has become an important tool for the study of inflammatory phenomena in the upper airway. Biochemical and cytologic information is relatively easily obtainable, and pharmacologic manipulations can be readily monitored. This article is of several studies aiming toward a more profound understanding of the mechanisms of allergic and nonallergic rhinitis by the use of laboratory-challenge procedures and nasal-lavage techniques. An early and a late reaction are detected clinically in the nose after antigen challenge of allergic individuals. In addition, the sensitivity to antigen significantly increases after the initial challenge, and this phenomenon is not obligatorily linked to the presence of a late-phase reaction (LPR). Inflammatory mediators, mostly mast cell- and/or basophil-derived, are detected in the nasal washes and correlate with the symptomatology in both the early and the late reactions. The allergen-induced LPR is marked by an early influx of eosinophils and, later, basophils and neutrophils. Elevation of major basic protein and histamine, but not prostaglandin D2, is detected during the LPR, giving evidence of active eosinophil and basophil participation. Systemic steroids can effectively suppress the clinical, biochemic, and cellular manifestations of antigen-induced LPR. Topical steroids have a similar effect but are also capable of suppressing the early reaction to antigen. A nonallergic form of rhinitis can be induced in the laboratory by nasal inhalation of dry air at freezing temperatures in individuals who report sensitivity to cold and windy environments.(ABSTRACT TRUNCATED AT 250 WORDS)

Environmental Exposure↗
PubMed1988

Wheal-and-flare reactions induced by allergen and histamine: evaluation of blood flow with laser Doppler flowmetry.

Dermal blood flow was evaluated after skin prick test with histamine and allergen in six patients with seasonal allergic rhinitis. Blood flow was registered continuously for 60 minutes after the test procedure with laser doppler flowmetry, which allows noninvasive measurements. Blood flow was measured close to the skin test in the wheal obtained, and at a greater distance from the prick in the flare reaction. Tests were performed with preloaded skin test needles with histamine and the appropriate allergen freeze-dried on the point of the lancet, as well as with the appropriate negative control. The prick test procedure, by itself, induced a transient increase in blood flow that was normalized again after 9 minutes for the closest measurement. Histamine induced a rapid increase in blood flow in both the flare and wheal reaction that was normalized after about 45 minutes. The increase was significantly higher in the flare compared to the wheal for the time points from 6 1/2 to 13 minutes. Allergen induced a similar increase in blood flow. However, the increase was not noticeable until 2 1/2 minutes after the allergen application and was not completely abolished within 60 minutes. Furthermore, the difference between the flare and wheal reaction, with the higher values for the flare reaction, was present for a longer period of time than for the equivalent histamine measurements. In conclusion, laser doppler flowmetry appears useful for continuous evaluation of vascular changes induced at skin prick tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Allergen-induced hyperreactivity is not a feature of dermal immediate allergic reactions--in contrast to reactions of airways mucosa.

Allergen challenges of airway mucosa are commonly followed by an increased sensitivity to rechallenge with allergen. In the lower airways this phenomenon has been associated with the late phase of allergic airway reactions, which in turn has been suggested as a link between anaphylaxis and continuous allergic airway disease. The aim of the present investigation was to explore further the phenomenon of allergen-induced hyperreactivity and to see whether it was possible to induce such a reaction in the skin. Twenty-six patients with seasonal allergic rhinitis due to birch and/or grass pollens were studied in the pollen-free winter months. Nine of these patients had previously demonstrated an increased reactivity following allergen challenge in the nose, and nine of the patients had cutaneous allergen-induced late-phase reactions to the allergen tested. Skin-prick tests were performed with pollen allergen, histamine, and a negative control. The areas of the weal-and-flare reactions were measured 15 min after the tests were set. Any late-phase reactions were recorded 6 hr after the skin challenge. The subjects were re-tested with allergen and histamine 24 hr after the initial prick test within the area of the corresponding weal from the previous day. In contrast to previous challenges of human airway mucosa, where the same time interval was used, we found no increased responsiveness to rechallenge as compared with the initial allergen challenge. This was true, even if only the subgroups with previously demonstrated nasal allergen-induced hyperreactivity, or cutaneous late-phase reaction were evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Long-term safety of budesonide nasal aerosol: a 5.5-year follow-up study.

The effects of prolonged treatment with intranasally applied budesonide was studied in twenty-four patients with perennial allergic or non-allergic rhinitis. Patients on continuous treatment were followed up for 5.5 years. At entry and follow-up visits, rhinoscopic findings, nasal symptom scores, blood chemistry, haematology, urine analysis and determination of plasma cortisol levels, before and after stimulation with ACTH (Synacthen, Ciba-Geigy AG, Basel, Switzerland), were registered. Biopsies of the nasal mucosa were taken before entry into the study, after 1 year of treatment, and after varying time intervals ranging from 2.5 to 5.5 years during the treatment. The biopsy specimens were examined blindly by an independent pathologist. The analyses revealed no histopathological changes in the nasal mucosa. All nasal symptom parameters assessed by the patients were significantly reduced from the baseline during the entire follow-up period. No clinically significant changes in the haematological and blood chemistry parameters were observed. Plasma cortisol analyses before and after challenge with ACTH revealed no influence on the hypothalamic pituitary adrenal (HPA) axis. The present study suggests that intranasal budesonide in the dose of 200-400 micrograms/day is also a safe treatment for prolonged treatment of perennial rhinitis.

Adolescent↗
PubMed1988

Immediate and late phase allergic cutaneous reactions are not inducers of unspecific or specific local hyperreactivity.

The present study evaluates the possibility of allergen-induced unspecific and specific dermal hyperreactivity with special reference to the presence of late cutaneous reactions and allergen-induced nasal hyperreactivity. Twenty-six patients with strictly seasonal allergic rhinitis participated. All had a positive skin prick test for birch (Betula verrucosa) and/or timothy (Phleum pratense). Ten patients had previously displayed an allergen-induced nasal hyperreactivity and six patients a late cutaneous reaction. An initial skin prick test with a relevant pollen allergen was done in triplicate. The immediate skin reactions were recorded after 15 min and any late-phase reaction after 6 h. Twenty-four hours later the patients were retested. The same pollen allergen was sited in the first flare reaction from the previous day. A histamine prick test was sited in the weal as well as in the third reaction from day 1. A histamine control was also performed in a previously unaffected area. The allergen-induced weal reactions decreased significantly at rechallenge compared with the results from the previous day (P less than 0.05). The histamine tests resulted in similar skin reactions regardless of whether or not they were done on a previous allergen test site. This was true for both specific and unspecific reactions when the subgroups of patients with previously demonstrated allergen-induced nasal hyperreactivity or late-phase skin reactions were evaluated separately. These results indicate that allergen-induced hyperreactivity is not a general feature of allergic inflammation but is a phenomenon restricted to specific sites, such as the airway mucosa.

Adult↗
PubMed1988

Secretory activity of nasal mucosal mast cells and histamine release in hay fever.

Although theoretical considerations and experimental evidence implicate the mast cells in the pathophysiology of the immediate type hypersensitivity reaction, the evidence of their active participation in human allergic disease is still fragmentary. We have therefore sought evidence of mast cell activation in allergic mucosal disease using strictly seasonal allergic rhinitis as a model. Twelve patients with birch pollen-induced hay fever were examined before and well into the birch pollen season. Allergen exposure was monitored by pollen counts and the degree of symptoms registered daily. Small surgical biopsies and mucosal imprints were obtained from each patient before and during the season. Mast cells were analysed by light and electron microscopy and mucosal histamine was measured using a sensitive HPLC assay. We found a reduction in the number of mast cells in the nasal mucosa during pollen exposure (p less than 0.05) but no significant reduction of the histamine content. There was a correlation between the nasal mucosal mast cell density and histamine content before the pollen season (r = 0.76; p less than 0.01), but no such correlation was found during the period of pollen exposure (r = 0.19; n.s.). This finding points to secretory activity by the mast cells during the pollen season and to the appearance of a non-mast cell pool of tissue histamine. Evidence for a secretory activity of the mast cells during the pollen season was also confirmed by electron microscopy. In addition, we found a strong correlation (r = 0.77; p less than 0.01) between the histamine content of the nasal mucosa during the pollen season and the degree of nasal symptoms. The number of epithelium-associated mast cells found on mucosal imprints prior to the pollen season showed a strong correlation with the symptoms experienced later during the period of pollen exposure (r = 0.83; p less than 0.01). Taken together these observations indicate that the mast cell has a pathogenetic role in continuous allergic airway disease and re-emphasizes the role of histamine in the induction of the symptoms of allergic rhinitis.

Adult↗
PubMed1988

The influx of inflammatory cells into nasal washings during the late response to antigen challenge. Effect of systemic steroid pretreatment.

Previous studies have demonstrated symptoms and mediator release occurring as long as 11 h after nasal challenge with antigen in selected allergic subjects. Pretreatment with systemic steroids reduced symptoms and mediators including histamine, TAME-esterase activity, and kinins. The aims of the present study were to characterize the cell influx during the late-phase response to antigen challenge and to determine the effect of pretreatment with systemic steroids on this response. We examined cytospin slides of nasal washings obtained before and hourly for 11 h after nasal antigen challenge in 10 asymptomatic allergic subjects with a history of seasonal rhinitis and 5 normal, nonallergic subjects. Allergic subjects received oral prednisone (20 mg 3 times a day) or placebo in a random, double-blind crossover manner for 2 days before each of 2 challenges 1 month apart. On placebo days, a mixed cell influx occurred in allergic subjects during the late response that was 50-fold greater than the cell influx in the nonallergic control subjects (p less than 0.005). During the first 3 h after antigen challenge, eosinophils (p less than 0.005), but not neutrophils or mononuclear cells, were observed. During the late phase (4 to 11 h), neutrophils, eosinophils, and mononuclear cells were all increased. Oral steroid pretreatment blocked the influx of eosinophils (p less than 0.005), but not that of other cells. These data demonstrate an inflammatory cell influx associated with the nasal late-phase response and suggest an important pathogenetic role for the eosinophil.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Basophil influx occurs after nasal antigen challenge: effects of topical corticosteroid pretreatment.

Both the pattern of mediator release during the late-phase response (LPR) and the reduction of the LPR with corticosteroid pretreatment have suggested that basophils, not mast cells, represent the main source of histamine in the late response to nasal antigen challenge. We tested this hypothesis by examining alcian blue-stained cytospin slides of nasal washings obtained before and for 11 hours after nasal antigen challenge in 11 asymptomatic subjects with seasonal allergic rhinitis. In a double-blind manner, subjects received placebo or topical flunisolide (50 micrograms, each nostril, twice daily) for 1 week before antigen challenge. One month later, the challenge was repeated with the alternate pretreatment. On placebo-treatment days, a twelve-fold increase occurred in the number and a threefold increase in the percentage of alcian blue-stained positive cells in nasal washings in the LPR compared to baseline. At least 68% of these alcian blue-stained positive cells were basophils, as determined by light microscopic criteria. Alcian blue-stained cell influx correlated with increases in histamine levels in nasal washes (p less than 0.001). Topical steroid pretreatment blocked the influx of alcian blue-stained positive cells, as well as other inflammatory cells, including eosinophils, neutrophils, and mononuclear cells. Symptoms and mediator release were also blocked. These data demonstrate an influx of basophils and suggest that these cells are responsible for the histamine release observed in the LPR. Our findings indicate that pharmacologic control of basophil histamine release may represent a strategy for the treatment of a variety of chronic allergic diseases that are believed to resemble the LPR.

Administration, Topical↗
PubMed1988

Methods for obtaining specimens from the nasal mucosa for morphological and biochemical analysis.

The nose is the part of the airway system which is most easily accessible for morphological and pathophysiological evaluation of changes occurring as a response to various stimuli. During recent years several new atraumatic techniques for harvesting cells for morphological and biochemical analysis have been introduced, in addition to the more well known surgical biopsy procedures and nasal smears. Such techniques include nasal lavage, scrapings from the nasal mucosa, brush techniques and imprints. Several of these techniques allow repeated samplings, obtaining quantitative as well as qualitative information as to the cells present on the surface of, as well as within, the epithelial lining of the nasal mucosa. Some techniques provide the investigator with a method for obtaining information on the cellular content of certain biochemical markers such as histamine. The present review describes the merits and disadvantages of the old and new methods and provides guidelines as to when each method should be considered.

Biopsy↗
PubMed1988

Nasal mucosal blood flow after intranasal allergen challenge.

The nasal mucosal blood flow in patients with allergic rhinitis was determined at nasal allergen challenges with the 133Xenon washout method. Determinations were made in 12 subjects before and 15 minutes after challenge with diluent and increasing doses of allergen. The time course was followed in eight subjects by means of repeated measurements during 1 hour after a single allergen dose. Finally, the blood flow was measured after unilateral allergen challenge in the contralateral nasal cavity. A dose-dependent decrease in blood flow was found after nasal challenge with increasing doses of allergens, whereas challenge with diluent alone did not induce any changes. The highest allergen dose, which also induced pronounced nasal symptoms, resulted in a decrease in blood flow of 25% (p less than 0.001). The time-course study demonstrated a maximum decrease in blood flow 10 to 20 minutes after challenge and then a gradual return to baseline. Unilateral allergen challenge resulted in a decrease in blood flow in the contralateral, unchallenged nasal cavity, suggesting that part of the allergen-induced changes in blood flow were reflex mediated.

Adult↗
PubMed1987

Inhibition of mediator release in allergic rhinitis by pretreatment with topical glucocorticosteroids.

Patients with allergic rhinitis often have immediate symptoms after antigen challenge (the early-phase response), followed several hours later by a recurrence of symptoms (the late-phase response). Systemic glucocorticosteroids are known to inhibit the late-phase but not the early-phase response. We studied the effect of one week of pretreatment with topical (rather than systemic) glucocorticosteroids on the response to nasal challenge with antigen in a double-blind, randomized, placebo-controlled crossover study of 13 allergic patients who had previously had a dual response to nasal challenge. The patients were challenged with three 10-fold increments of allergen, producing an early response, and were then followed for 11 hours, encompassing the late response, before they were rechallenged with the lowest dose of allergen. We monitored their responses by means of symptom scores and measurements of the levels of histamine, tosyl-L-arginine methyl ester (TAME)-esterase activity, and kinins in nasal lavages. Topical glucocorticosteroids significantly reduced both the symptoms and the levels of histamine, TAME-esterase activity, and kinins in the early, late, and rechallenge allergic reactions. The fact that, in contrast to treatment with systemic glucocorticosteroids, prolonged pretreatment with topical glucocorticosteroids inhibited the early-phase response to antigen suggests that the route and duration of administration affect the mechanisms of action of the steroids. We conclude that inhibition of the early-phase as well as the late-phase response by topical glucocorticosteroids may provide an advantage over treatment with systemic glucocorticosteroids in patients with allergic rhinitis.

Administration, Topical↗
PubMed1987

Inhibition of the dermal immediate allergic reaction through prolonged treatment with topical glucocorticosteroids.

The effect of prolonged topical dermal glucocorticosteroid treatment on the immediate and late-phase allergic skin reaction was studied in a double-blind, randomized, placebo-controlled study. Seventeen patients with hay fever and with a positive skin test for timothy and/or birch pollen allergens were studied in a pollen-free season. Skin prick tests for these two allergens as well as a negative saline and a positive histamine control were made with a preloaded standardized prick test needle. The area of the induced wheal-and-flare reaction was measured 15 minutes after allergen application, and any induced late-phase responses were measured after 6 hours. After a baseline recording, the patients treated the volar aspect of one forearm twice daily with a cream of 0.05% clobetasol 17-propionate and the other forearm with the equivalent vehicle in a randomized, double-blind fashion. After 1 week the skin prick test was repeated on both arms. A statistically significant reduction of the allergen-induced wheal-and-flare response was found after active treatment as compared to control and pretreatment values. A reduction was also found in the histamine-induced flare but not the wheal reaction as compared to the control. A late-phase dermal reaction was found in six of the patients, and this was statistically significantly reduced by the glucocorticosteroid pretreatment. Thus, in similarity to findings in vivo on the human nose and bronchus, we found, in addition to the well-known glucocorticosteroid-induced reduction of the allergic late-phase response, an inhibition of the dermal immediate allergic reaction as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1987

Topical dermal anaesthesia inhibits the flare but not the weal response to allergen and histamine in the skin-prick test.

The effect of topical dermal anaesthesia on the immediate allergic skin reaction was evaluated in a double-blind, randomized, placebo-controlled study. Twenty-one patients with strictly seasonal allergic rhinitis, confirmed by a positive skin test for the respective pollen allergen, were studied in the pollen-free winter months. Skin-prick tests for one pollen allergen and histamine were performed after pre-treatment of the skin for 1 hr with an emulsion of lidocaine and prilocaine (EMLA) and the equivalent vehicle on different test sites. The skin-prick tests were made with a preloaded standardized test needle (Phazet). The area of the induced weal-and-flare reaction was measured and subsequently calculated with the help of a digitizer served by a microcomputer. The topical dermal anaesthesia induced a reduction of the flare response to histamine by 49% (P less than 0.01) and allergen by 21% (P less than 0.05). No reduction of the histamine- and allergen-induced weal response were noted. Our findings indicate that the treatment did not affect the allergen-induced release of inflammatory mediators and the vascular leakage induced by these mediators. However, this study seems to confirm earlier suggestions that the flare response is partly mediated through neural reflex activity as it was ameliorated by topical anaesthesia. Furthermore, from a clinical point of view, this study shows that it is possible to perform a valid skin test, without any associated itching and pain, if only the weal response is taken into account in the evaluation of the skin-prick test.

Adolescent↗
PubMed1987

The effect of a histamine synthesis inhibitor on the immediate nasal allergic reaction.

We studied the effect of alpha-fluoromethyl histidine, an irreversible histamine synthesis inhibitor, on the immediate nasal reaction to antigen challenge in a double-blind, placebo controlled, randomized, parallel study using 13 subjects. The patients received either active drug 100 mg twice daily or placebo, for 3 weeks. A nasal allergen challenge was performed before and after at weekly intervals. Symptoms at challenge were assessed and the levels of histamine, TAME-esterase activity and kinins were measured in nasal lavages before and after antigen challenge. Skin tests were also performed at weekly intervals. In addition, the urinary excretion of the main histamine metabolite, telemethylimidazole acetic acid, was measured before and after 3 weeks of treatment. The active treatment induced 60% reduction in histamine levels in the lavage fluids before and after antigen challenge, as well as a reduction in the histamine levels in the lavage fluids before and after antigen challenge, as well as a reduction in the main urinary histamine metabolite. However, no reduction was found in nasal symptoms obtained after antigen challenge. The levels of kinins and TAME-esterase activity were not significantly reduced.

Adult↗