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Biomedical subjects

U Pipkorn

Publications and source records attributed to U Pipkorn.

At least 91 records · Page 5Linked to original sources
PubMed1987

Topical levocabastine, a selective H1 antagonist, in seasonal allergic rhinoconjunctivitis.

Sixty-six patients with seasonal allergic rhinitis due to birch pollens, participated in an efficacy evaluation of topically applied, nasal and ocular, levocabastine, a highly selective H1 antagonist. A single blind comparison was performed between nasal levocabastine and flunisolide, a topical glucocorticoid preparation. Ocular levocabastine was compared with topical naphazoline/antazoline eye drops. Nasal and ocular symptom scores were recorded during a 31-day period. Pollen counts of birch pollens were done simultaneously. A global assessment of treatment efficacy was also made. In the comparison between the ocular treatments a significantly higher number of patients cited levocabastine excellent--it also had the advantage of fewer daily administrations. For nasal symptom scores the topical glucocorticosteroid therapy was in favour by number of sneezes. As for side effects, 44% of the patients complained of local irritation from naphazoline/antazoline eye drops or flunisolide nasal spray, but none with the levocabastine preparations. Topical levocabastine may provide an interesting alternative in the treatment of allergic rhinoconjunctivitis.

Administration, Intranasal↗
PubMed1987

Allergen-induced nasal hyperreactivity appears unrelated to the size of the nasal and dermal immediate allergic reaction.

It has been previously demonstrated in nasal challenge studies that there is an increased sensitivity to allergen following an initial allergen challenge. A similar feature has been demonstrated following natural allergen exposure in patients with seasonal allergic rhinitis. To further explore the characteristics of this "priming" phenomenon and its relationship to other expressions of their allergic airway disease, 28 hay fever patients with strictly seasonal disease were studied. Skin tests with the relevant pollen allergen and histamine were performed and the size of the immediate and late phase allergic reaction was determined. An initial nasal allergen challenge was followed by a rechallenge of the nose with allergen 24 h later using a lavage technique. Determinations of TAME-esterase activity, as a biochemical marker of the allergic reaction, were made in the returned lavage fluid. The number of sneezes was counted and nasal symptoms were also assessed using a scoring technique. 19 of 28 patients (67%), displayed an increased responsiveness at rechallenge with similar findings in terms of symptom scores and TAME-esterase measurements. The increase was statistically significant for the symptoms of nasal blockage, which increased from 0.7 +/- 0.1 (mean +/- SEM) to 1.1 +/- 0.2 (P less than 0.05), and nasal secretion which rose from 1.1 +/- 0.2 to 1.7 +/- 0.2 (P less than 0.01). A composite nasal symptom score which also took account of the number of sneezes, increased from 2.9 +/- 0.4 to 4.0 +/- 0.3 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Nasal mucosal mast cells and histamine in hay fever. Effect of topical glucocorticoid treatment.

Symptomatic seasonal allergic rhinitis has previously been found to be associated with a redistribution of mast cells from the subepithelial stroma to the epithelial lining and the surface of the nasal mucosa. The present study was designed in order to elucidate the interaction between topical glucocorticosteroids, effective in the treatment of allergic rhinitis, and the migration of mast cells described earlier. Six patients treated prophylactically in the nose with budesonide were studied. Imprints and biopsies from the nasal mucosa were taken 2-3 weeks before and 2-3 weeks into the birch pollen season. The biopsies were used for light microscopy and tissue histamine determination. The morphologic studies showed, also in the actively treated patients, an increased number of metachromatically stained cells on the nasal mucosal surface of the same order of magnitude as previously reported for untreated patients. We did, however, find a decrease in the histamine content of the nasal mucosa, which was not associated with a decrease in the number of mast cells. Together with similar previous findings in the unstimulated allergic nasal mucosa these results suggest that glucocorticosteroids induce a decrease in the mast cell histamine pool, possibly due to an inhibition of the intracellular synthesis of histamine. This effect might contribute to the clinically beneficial effect of topical glucocorticosteroids in the treatment of hay fever.

Administration, Topical↗
PubMed1987

Effect of short-term systemic glucocorticoid treatment on human nasal mediator release after antigen challenge.

The effect of systemic glucocorticoid treatment on early- and late-phase nasal allergic reactions after allergen challenge was determined in a double-blind, cross-over study in 13 allergic individuals. The subjects were pretreated for 2 d before challenge with 60 mg prednisone per day or a matching placebo. A previously described model using repeated nasal lavages for measuring mediator release in vivo was utilized. Symptom scores obtained repeatedly before, during, and after the challenge and the number and timing of sneezes were recorded. The mediators measured were histamine. N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity, kinins, PGD2, and LTC4/D4. Albumin was also measured as a marker of plasma transudation. Blood samples were taken for determination of total number of white blood cells, differential count, and total blood histamine content. No effect of steroid therapy was found on the appearance of symptoms or any of the mediators, except a reduction in kinins, in the early phase of the allergic reaction. However, in the late phase, the prednisone reduced the number of sneezes (P less than 0.01), as well as the level of histamine (P less than 0.05), TAME-esterase activity (P less than 0.05), kinins (P less than 0.05), and albumin (P less than 0.05). Only low levels of leukotrienes were found in the late phase, but the quantities of these mediators seemed to be decreased by the glucocorticoid treatment (P = 0.06). PGD2 did not increase during the LPR and thus was not affected by glucocorticosteroids. The immediate response to a second challenge 11 h after the first was also evaluated. Whereas the appearance of mediators was enhanced over the initial response to the same challenge dose in placebo-treated subjects, this enhancement was abrogated after prednisone treatment. As this dose of drug is known to be clinically effective in treating hay fever, the present study confirms the earlier findings of others that short-term systemic glucocorticoid treatment inhibits the late phase but not the immediate phase of antigen challenge. Furthermore, secondary enhancement of immediate responses is inhibited. This study shows that glucocorticoids inhibit the generation or release of inflammatory mediators during the late reaction and the physiologic response.

Administration, Intranasal↗
PubMed1986

Substance P and human nasal mucociliary activity.

Substance P (SP), a potent inflammatory agent, has been found in sensory nerve fibres in the nasal mucosa in several experimental animals as well as in man. It may participate in the inflammatory response as part of the mucosal defence against foreign materials. In experimental animals SP has been found to increase mucociliary in airway mucosa. The present study was performed in order to find out the relationship between topically applied SP and nasal mucociliary function in humans. Thirteen healthy volunteers were challenged with 65 micrograms SP or placebo in a randomized cross over fashion and mucociliary transport time was determined each time using the saccharine dye test. The dose of SP was chosen after an open dose-response study. No statistically significant change in the mucociliary transport time was found after challenge with SP as compared to placebo. The possible reasons for this are discussed.

Adult↗
PubMed1986

Influence of topical beclomethasone dipropionate suspension on human nasal mucociliary activity.

The local effect of an aqueous suspension of beclomethasone dipropionate on human nasal mucociliary clearance was studied in 14 healthy volunteers. A triple blind, randomized, placebo controlled, cross-over design was utilised. Measurements of mucociliary clearance were made before treatment, after a single dose and after one week of continuous treatment either with placebo or active substance, utilising the saccharine-dye test. No change in mucociliary clearance was found after treatment with beclomethasone dipropionate or placebo suspension.

Administration, Topical↗
PubMed1986

The pharmacologic control of mediator release from human basophils and mast cells.

Insight into the pathogenesis of human allergic and inflammatory disorders has been obtained through a combination of in vitro and in vivo studies. These investigations have demonstrated that human basophils and mast cells release mediators after nonimmunologic as well as immunologic activation in vitro and in vivo: nonimmunologic triggers include changes in osmolarity. Although these cells share many properties, including the presence of high-affinity receptors for IgE on their cell surface, the presence of histamine in granules, the ability to generate and release large quantities of leukotriene C4 (LTC4) after activation, and the ability of several pharmacologic agents including phospholipase inhibitors, acetylene analogues of arachidonic acid (ETYA, ETI), methylxanthines, prostaglandin E2 (PGE2) beta-agonists, and cyclic AMP to inhibit mediator release, they also display notable differences. Human lung mast cells generate and release large quantities of prostaglandin D2 (PGD2) after activation; basophils generate no known cyclooxygenase product. Indomethacin, arachidonic acid, and 5-hydroperoxyeicosatetraenoic acid (5-HPETE) all enhance histamine and LTC4 release from human basophils; no effect is seen with human lung mast cells. Overnight incubation of basophils with glucocorticoids produces a marked inhibition of mediator release; this treatment does not affect the release of mast cell mediators. These in vitro observations are consistent with our in vivo observations and our hypotheses concerning the importance of these cells in allergic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1986

Intraepithelial migration of nasal mucosal mast cells in hay fever.

Mast cells were studied by light microscopy in mucosal imprints and in biopsies of nasal mucosa of 12 birch pollen allergic individuals before and during the pollen season, using techniques optimized for the demonstration of mucosal mast cells. We also measured the histamine content of nasal mucosa, whole blood and plasma, and counted the numbers of circulating blood basophils. Before the pollen season the nasal mucosa was found to contain many mast cells located in the mucosal connective tissue stroma, and very few cells with basophilic and metachromatic granules were found in mucosal imprints. During the pollen season there was a redistribution of mast cells into the epithelium, many such cells now being recovered in mucosal imprints. The total number of mucosal mast cells counted in tissue sections did not change significantly with the onset of the pollen season, suggesting a redistribution of mucosal mast cells by migration. Judged by morphologic appearance and naphthol-AS-D chloroacetate esterase activity, the intraepithelial mast cells found in tissue sections had rather the properties of tissue mast cells than of blood basophils, and only a few of the basophilic cells of the imprints had a morphology compatible with blood basophils. The histamine content of the mucosa, as well as histamine levels of whole blood and plasma, and circulating blood basophil numbers did not change significantly in relation to the pollen season. These findings suggest that an intraepithelial migration of mucosal mast cells is part of the allergic mucosal response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Intraepithelial migration of mucosal mast cells in hay fever: ultrastructural observations.

Evidence has been presented suggesting that a migration of nasal mast cells from the mucosal connective tissue stroma into the epithelium is part of the mucosal response in birch pollen allergy. In a previous study, the identification of these intraepithelial cells as tissue mast cells rather than blood basophils was based on light microscopical morphology and histochemistry. We have now studied the ultrastructure of these cells in mucosal biopsies taken before and during the birch pollen season. Intraepithelial cells with basophil or metachromatic granules were only observed in biopsies taken during the season. Some of these cells had the ultrastructural appearance of tissue mast cells, including cytoplasmic lipid droplets and a granular substructure composed of multilamellar arrays and scrolls, serving to distinguish human mast cells from blood basophils. The ultrastructural traits of the remaining cells were heterogeneous, some reminiscent of human blood basophils, others of globule leucocytes of other species, but entirely typical blood basophils could not be identified. The results thus support our previous suggestion that a migration of mucosal mast cells from the connective tissue stroma into the epithelium is part of the human allergic mucosal response. It cannot be determined whether the ultrastructural heterogeneity of these cells is the result of an adaptation to the intraepithelial environment of one single mast cell type or to the existence of an ultrastructurally distinct mucosal mast cell.

Basophils↗
PubMed1985

A double-blind evaluation of topical levocabastine, a new specific H1 antagonist in patients with allergic conjunctivitis.

Forty patients suffering from allergic conjunctivitis, due to birch pollen, participated in a double-blind parallel group comparison between levocabastine (a potent new specific histamine (H1) antagonist) and placebo, both given as eye drops. Symptom scores were recorded during a 4-week period. A 1-week run-in period was followed by a 3-week treatment period. To enable a fair evaluation of the treatment effect on the ocular symptoms only, all patients were treated with topical nasal glucocorticoids for possible rhinitis symptoms during the whole study period. Plasma levels of levocabastine were determined in all subjects at the end of the 3 weeks' treatment period. Pollen counts for birch pollen were followed simultaneously. The evaluation of the symptom score cards revealed a significant reduction of ocular symptoms following use of the active compound. The resorption of the active substance through the conjunctiva was low. In accordance with the present trend of more topical treatment for allergic rhinitis, levocabastine may constitute a valuable compound for the topical treatment of allergic conjunctivitis.

Adolescent↗
PubMed1985

Mucociliary transport in the human nose. Effect of topical glucocorticoid treatment.

The effect of topical budesonide on the human mucociliary transport in the nose was investigated utilizing the saccharin-dye test in 10 healthy volunteers. Measurements were made before treatment, after a single dose and after one week continuous treatment with either placebo or active substance. The design of the study was double blind, randomized and cross-over. A single dose of placebo or budesonide did not alter the mucociliary transport as compared to pretreatment values. A trend towards decrease of mucociliary transport was noted after one week treatment with the active drug, a trend that reached statistical significance in the comparison between the 1 h value and the 1 week value.

Administration, Topical↗
PubMed1985

Mast cells on the surface of the mucous membrane--a general feature of inflammatory reactions in the nose?

A redistribution of mast cells towards the epithelial lining of the nasal mucous membrane has been shown to be a part of the allergic inflammatory reaction in hay fever. This results in an increased number of metachromatically stained cells on the surface of the mucous membrane. The involvement of mast cells in other inflammatory reactions in the human nose is not clarified and this may partly be due to methodological difficulties. Utilizing a recently developed imprint technique, specimens were taken from patients with infectious rhinosinusitis in acute and chronic stages. The total number of mast cells on 2 cm2 of the imprint area were counted. Mast cells in extremely low numbers were found in 5 out of 26 patients. Our results indicate that mast cell migration is not present in patients with infectious inflammatory reactions of the nasal mucous membrane.

Adult↗
PubMed1984

A method for the preparation of imprints from the nasal mucosa.

Important immunological reactions take place on the surface of mucosal membranes. Improved methods for the sampling and quantitative study of the cells taking part in these reactions are therefore desirable. We here describe a new technique for the preparation of imprints from the nasal mucosa. The method utilizes a plastic film coated with a thin layer of an albumin-glycerol mixture to improve cell adherence to the surface. The membrane is gently pressed onto a defined portion of the mucous membrane. Fixation and staining procedures are performed on the plastic film, which is then mounted on a slide and covered by a coverslip. The preparations have excellent optical properties and specific cell types can be easily studied, quantified and related to the specific area of the mucosa from which the imprint was taken.

Cell Adhesion↗
PubMed1984

Effect of disodium chromoglycate on changes in nasal airway resistance induced by platelet activating factor.

Thirteen healthy subjects participated in a double blind, randomized, cross-over investigation of whether or not intranasal disodium chromoglycate could block the change in nasal airway resistance induced by platelet activating factor (PAF). Placebo or active drug was given for 3 days before intranasal challenge with PAF. Nasal airway resistance before and at intervals after challenge was determined with a rhinomanometer. Pretreatment with disodium chromoglycate blocked the decrease in nasal airway resistance induced by PAF. This indicates an alternative mode of action of disodium chromoglycate in the treatment of allergic airway diseases.

Adult↗
PubMed1984

A single blind clinical comparison between 2 preparations of budesonide in the treatment of seasonal allergic rhinitis.

A comparative study was carried out in 118 patients suffering from seasonal allergic rhinitis in order to evaluate possible differences between two different preparations of budesonide with regard to effect and adverse reactions. The glucocorticoid was supplied either as a freon propellant device (Rhinocort) or as a water solution in a mechanical pump spray. The freon aerosol was administered in a daily dosage of 400 micrograms. The water solution was administered in daily dosages of 400 micrograms or 200 micrograms. The patients scored their nasal and ocular symptoms daily for 1 month, and pollen counts were registered over the same period. The drugs employed in the study provided good control of the nasal symptoms. The daily dosage of 400 micrograms in both preparations proved more efficacious than the daily 200 micrograms dose in the nasal pump spray. No difference was found between the delivery systems when the same daily dosage was used. The number of adverse reactions was low and insignificant in all 3 treatment groups.

Administration, Intranasal↗
PubMed1984

Effect of platelet activating factor on the human nasal mucosa.

In order to determine the effect of PAF-acether on the vascular bed in the human nose, 11 healthy volunteers were studied. Rhinomanometry was performed to determine the effect on the capacitance vessels, and the 133Xe wash-out method enabled determination of the mucosal blood flow, regulated mainly by the resistance vessels. These measurements were made before and after topical administration of PAF-acether in three different doses; 0.26 micrograms, 2.6 micrograms and 26 micrograms per nostril. The results indicate that PAF-acether induces a dose-dependent vasoconstriction of the capacitance vessels and a reduction in mucosal blood flow. That PAF-acether should be a principal mediator in the allergic reaction in the human nose is not supported by these findings.

Adult↗
PubMed1984

A comparative trial testing budesonide and flunisolide nasal sprays in patients with seasonal allergic rhinitis.

A group comparative study was carried out in 60 patients suffering from seasonal allergic rhinitis in order to evaluate the effects and side effects of the recently introduced glucocorticoids budesonide and flunisolide delivered as nasal sprays. Symptom scores for nasal and ocular symptoms as well as pollen counts were registered daily for one month. Both treatments provided excellent control of nasal symptoms. However, a significantly higher number of patients in the flunisolide group complained about nasal irritation.

Adolescent↗