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Biomedical subjects

N Mygind

Publications and source records attributed to N Mygind.

At least 19 recordsLinked to original sources

Intranasal administration of insulin with phospholipid as absorption enhancer: pharmacokinetics in normal subjects.

The pharmacokinetics of intranasal insulin containing a medium-chain phospholipid (didecanoyl-L-alpha-phosphatidylcholine) as absorption enhancer, was studied in normal volunteers by measuring plasma glucose, insulin, C-peptide, and glucagon. Eleven fasting subjects received 4 U insulin intravenously, 6 U subcutaneously, or three doses intranasally (approximately 0.3 U kg-1, 0.6 U kg-1, 0.8 U kg-1) in random order on five separate days. Intranasal insulin was absorbed in a dose-dependent manner with a mean plasma insulin peak 23 +/- 7 (+/- SE) min after administration. Mean plasma glucose nadir was seen after 44 +/- 6 min, 20 min later than following intravenous injection. Furthermore, intranasal administration of insulin resulted in a faster time-course of absorption than subcutaneous injection, with significantly reduced intersubject variation (p less than 0.001). Bioavailability for the nasal formulation was 8.3% relative to an intravenous bolus injection when plasma insulin was corrected for endogenous insulin production estimated by C-peptide. A dose-dependent suppression of C-peptide and stimulation of glucagon secretion occurred after intranasal administration of insulin. Nasal irritation from spraying was absent or slight.

Absorption

Powder administration of pure budesonide for the treatment of seasonal allergic rhinitis.

The objective of this study was to compare the efficacy and safety of a pure powder formulation of budesonide, delivered from a new multi-dose dispenser for nasal drug application, with the commercially available budesonide pressurized aerosol, and with placebo. Of 116 patients with grass pollen-induced allergic rhinitis, 112 finished the study, which comprised a 4-week treatment period, preceded by a 1-week run-in period. The patients were randomized to four parallel treatment groups: budesonide powder 400 micrograms daily; budesonide powder 800 micrograms daily; budesonide aerosol 400 micrograms daily; and placebo powder. Treatment was given once daily in the morning. The study was double-blind regarding comparison between budesonide powder and placebo. Assessment of efficacy, made by comparing mean scores of nasal symptoms and use of rescue medication, showed equal efficacy of all three budesonide groups compared with placebo. There were no differences between budesonide-and placebo-treated groups with regard to side effects. Budesonide treatment had no demonstrable effect on the HPA-axis assessed by measurement of 24-h urine cortisol. We conclude that budesonide, delivered as pure powder from a multi-dose dispenser, is effective and safe for the treatment of seasonal allergic rhinitis. This new formulation is a good alternative to the commercially available preparations, as it does not contain carrier gas, preservatives or lubricants.

Administration, Topical

Allergen-induced increase of eosinophil cationic protein in nasal lavage fluid: effect of the glucocorticoid budesonide.

It was our aim to study the effect of nasal allergen provocation on the concentration of eosinophil cationic protein (ECP) in nasal lavage fluid, with and without glucocorticoid pretreatment. Twenty grass-pollen sensitive volunteers were provoked outside the pollen season on 2 consecutive days after pretreatment for 2 weeks with the glucocorticoid, budesonide, as a nasal spray (400 micrograms/day) and with placebo with a double-blind, crossover design. Nasal lavage fluid was repeatedly collected during a 10-hour period to study both early and late-phase responses. 99mTechnetium-albumin was added to the lavage fluid, making it possible to calculate the amount of secretion and the degree of dilution. The results were as follows: (1) There was no correlation between ECP concentration and dilution factor in the individual samples. (2) The mean concentration of ECP in lavage fluid from untreated, prechallenge noses was 400 micrograms/L. (3) The ECP level did not increase during the early phase response. (4) There was a late occurring increase in the ECP concentration (6 to 24 hours). (5) This increase was completely inhibited by budesonide pretreatment. (6) The glucocorticoid therapy also reduced the prechallenge ECP concentration. In conclusion, allergen provocation in the nose results in a late occurring increase of ECP in nasal lavage fluid, and one of the therapeutic effects of topical glucocorticoid therapy may be an inhibition of the allergen-induced increase of this cytotoxic molecule.

Adult

Nasal polyposis.

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Cell Degranulation

Nasal inhalation of the glucocorticoid budesonide from a spacer for the treatment of patients with pollen rhinitis and asthma.

Glucocorticoid sprays are increasingly used for the treatment of allergic rhinitis and asthma. This therapy is highly effective, and side effects are few and mild. It was the aim of the present study to evaluate a physiological nasal inhalation technique, which results in airway deposition of the steroid molecule similar to that of inhaled allergen particles. Thirty adults with grass pollen-induced rhinitis and asthma inhaled the steroid molecule budesonide through the nose from a pressurized aerosol attached to a spacer device. Compared with inhalation of placebo, the treatment resulted in a significant reduction of nasal symptoms (P = 0.005), of bronchial symptoms (P = 0.005), but not of eye symptoms. In addition, nasal peak inspiratory flow (P = 0.0003) and oral peak expiratory flow (P = 0.02) increased. There was no difference between budesonide and placebo with regard to local side effects, such as nose bleeding, hoarseness, and irritation in mouth and throat. It is concluded that nasal inhalation of a steroid from a spacer offers effective therapy of pollen rhinitis and asthma without significant local side effects. This therapeutic modality may have advantages over the ordinarily used nasal and bronchial spray treatment in patients with both rhinitis and asthma, especially when conventional spray therapy is associated with local side effects.

Administration, Topical

Beclomethasone dipropionate versus flunisolide as topical steroid treatment in patients with perennial rhinitis.

After a 2-week run-in period 23 atopics and non-atopics with perennial rhinitis were treated with intranasally nebulized aqueous flunisolide or aqueous beclomethasone dipropionate in a randomized, double-blind cross-over study, each treatment period being 4 weeks. Before and after each treatment period daily rhinitis symptoms were recorded, and additional determination of nasal airway resistance was performed by posterior rhinomanometry. No statistically significant difference between drugs was observed for any effect parameter recorded, and furthermore no difference in patient preference for either drug was found. It is concluded that both steroids are effective for the improvement of nasal airway in patients with perennial, atopic and non-atopic rhinitis.

Administration, Intranasal

Intranasal ipratropium: literature abstracts and comments.

Eighty micrograms of the topically active parasympatholytic drug ipratropium were applied intranasally four times daily in 20 adults with perennial rhinitis and severe watery rhinorrhoea in a double-blind controlled cross-over trial. There was a significant reduction in nasal hypersecretion during ipratropium treatment. Fourteen patients preferred the ipratropium period, three the placebo period and three had no preference. There were no systemic or local side effects. Ipratropium was effective also in patients resistant to glucocorticoids, sodium cromoglycate and antihistamines. As the drug works immediately it can also be used before exposure to known provocating factors. It is concluded that continuous use of this new medication is of value in the management of severe rhinorrhoea in patients with perennial rhinitis, and that the occasional use is helpful in subjects with infrequent attacks of nasal hypersecretion.

Administration, Inhalation

Leukotriene C4 and histamine in early allergic reaction in the nose.

We have examined the measurements of LTC4 and histamine in nasal lavage fluids and blown secretions as a possible model of the early mediator events during nasal allergy. A nasal challenge with grass pollen extract was undertaken on two separate occasions in 20 patients with a history of seasonal rhinitis and a positive immediate skin test to grass pollen. A 2 ml nasal lavage was performed before allergen challenge, and blown secretion collected separately 15 min after the provocation, followed by a final 2 ml nasal lavage. The dilution of nasal secretion by the lavage fluid was determined using 99mTc-labelled albumin as an exogenous marker added to the fluid. The amounts of admixture in the nasal lavages did not correlate to the concentrations of LTC4 and histamine, indicating that the variable amounts of nasal secretion in nasal lavage do not constitute a confounding variable for measurements of LTC4 and histamine. In the pre-challenge lavages, the median concentrations, of LTC4 and histamine were 1.7 and 52 nmol/l respectively. Following allergen challenge neither LTC4 nor histamine measured in nasal lavage showed any significant change from pre-challenge baseline values. However, measurements of both mediators in the blown secretion showed a significantly higher concentration than in the pre- or post-challenge lavage samples, compatible with transitory release during the acute allergic reaction. However, it seems doubtful whether measurements of LTC4 or histamine can be compared between blown secretion and nasal lavage fluid, even if the dilution factor is disregarded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of nasal allergen challenge on serotonin, substance P and vasoactive intestinal peptide in plasma and nasal secretions.

We have studied the changes in concentration of serotonin, substance P, and vasoactive intestinal peptide (VIP) in plasma following a nasal allergen provocation in 14 grass pollen-allergic subjects; in five the urinary excretion of serotonin and 5-hydroxy-indolyl-acetic acid (5-HIAA) was also measured. In addition, the concentration of serotonin and substance P was measured in nasal secretions following nasal challenge with allergen and methacholine. The results showed an allergen-induced increase in free plasma serotonin (P less than 0.01) and no change in platelet serotonin, urinary serotonin and urinary 5-HIAA. The plasma substance P level tended to fall (P greater than 0.1), while plasma VIP increased significantly (P less than 0.02). In nasal secretions, there were measurable levels of serotonin in all samples and of substance P in all but one. There was no difference between the concentrations of serotonin and substance P in secretions collected after allergen challenge and after methacholine challenge. For both substances, the secretion median value was comparable to that of plasma. Symptom reduction by topical and systemic pretreatment with a serotonin- and VIP-antagonist before nasal allergen provocation is necessary to define the role of these two agents in allergic rhinitis.

Adolescent

Lymphocyte subsets in normal airway mucosa of the human nose.

The distribution and number of lymphocytes, monocytes/macrophages, and cells expressing HLA-DR antigen were studied in frozen biopsy sections of nasal mucosa from 40 healthy adults, using monoclonal antibody avidin-biotin immunoperoxidase techniques. The lymphocyte to monocyte/macrophage ratio was estimated to be 10:1; the T cell to B cell ratio was 3:1; and the T helper/inducer cell to T suppressor/cytotoxic cell ratio averaged 2.5:1. Regional differences were observed with a relatively increased number of T suppressor/cytotoxic cells around submucosal glands, and a relatively large number of B cells in lymphocyte aggregates in the lamina propria. The HLA-DR antigen was expressed in epithelial cells, suggesting involvement of surface epithelium of human airway in local immune responses.

Adult

Cold air-induced rhinorrhea and high-dose ipratropium.

A high dose of the cholinoceptor antagonist ipratropium bromide, in the form of a nasal spray, was tested on cold air- and hot soup-induced rhinorrhea in order to determine to what extent these types of rhinorrhea are reflex-mediated hypersecretions from nasal glands. Fourteen normal volunteers were examined in a placebo-controlled study. A single dose of ipratropium bromide (400 micrograms) caused a 73% reduction of cold air-induced rhinorrhea and a 66% reduction of hot soup-induced rhinorrhea. It is concluded that a major part of the nasal discharge induced by these stimuli is reflex-mediated, and consequently may be treated by a cholinoceptor antagonist, such as ipratropium.

Administration, Intranasal

Influence of experimental rhinitis on the gonadotropin response to intranasal administration of buserelin.

The influence of experimental rhinitis on the absorption of buserelin, measured as the serum luteinizing hormone (LH) response, has been investigated. A single dose of 200 micrograms buserelin was given to 24 healthy male volunteers after induction of experimental rhinitis with histamine and after use of a saline spray (placebo control). Except on one occasion, when the pump-spray apparently was incorrectly operated, serum LH concentration rose after buserelin. There was no difference in the LH response between histamine-induced rhinitis and saline controls. It was concluded that intranasal application of buserelin represents a reliable mode of application and that modification of the administration route or a change in the dosage schedule during naturally-occurring nasal inflammations, such as the common cold and allergic rhinitis, is unnecessary in patients undergoing chronic treatment with intranasal buserelin, e.g. for prostatic cancer, endometriosis, precocious puberty, and contraception.

Absorption

Ordinary and high-dose ipratropium in perennial nonallergic rhinitis.

The aim of the present study was to test the efficacy of the topically active cholinoceptor antagonist, ipratropium, in the treatment of rhinorrhea in perennial nonallergic rhinitis, with special reference to identification of subgroups of responders and increased efficacy from high-dose therapy. Thirty-six adult patients with watery rhinorrhea as a dominant symptom completed the study, which consisted of a 2-week run-in period followed by two 3-week treatment periods with placebo and ipratropium in an ordinary dosage (80 micrograms four times a day) in a double-blind, crossover design, and, finally, an open 2-week period with high-dose therapy (400 micrograms four times a day). The number of nose blowings was 47% lower during treatment with ipratropium in the ordinary dosage than during the placebo period (p less than 0.001). There was an additional reduction during high-dose therapy that was slight but statistically significant (p less than 0.05). Ipratropium had no effect on the number of sneezes or on nasal blockage index. During ordinary-dose therapy, side effects were slight and confined to the nose, whereas the high-dose therapy caused unpleasant nasal dryness and, in a few cases, systemic side effects. It was not possible to separate responders from nonresponders by case history, physical examination, or nasal methacholine testing. It is concluded that intranasal ipratropium is effective in the treatment of watery rhinorrhea in perennial nonallergic rhinitis and that 320 micrograms a day is sufficient in most patients.

Adult

Measurement of secretion in nasal lavage.

1. The amount of admixture in nasal lavage fluids was determined by addition of 99mTc labelled albumin, providing a correction factor for measurements of cellular material and humoral substances in nasal lavage return as well as a quantitative measure of nasal secretions. 2. Albumin was chosen as marker molecule, since only negligible amounts were absorbed or adsorbed to the mucosa during the nasal lavage. 3. Labelling of the albumin with 99mTc ensured an accuracy of measurements only limited by the precision of the weighing. The isotope allowed for the determination of the amount of admixed secretion to be carried out on the whole sample of lavage fluid, thereby avoiding the necessity of complete admixture between marker and lavage fluid which would be pertinent to marker molecules measured chemically. The radiation from a nasal lavage is minimal and the procedure is fully acceptable for repeated use in humans. 4. The nasal lavage technique adopted allowed the return of 99.2% (median value) of the instilled volume. The area irrigated was visualized on a gamma-camera, and was demonstrated to cover an area larger than the area reached by challenge from a pumpspray, i.e. a large part of the nose, yet not the oropharynx. 5. A dose related increase in nasal secretion harvested by the nasal lavage in 10 persons challenged with histamine chloride could be demonstrated by this technique. 6. It is concluded that the use of 99mTc-albumin in a nasal washing provides a safe, simple and quick method for determination of the admixed nasal secretion with a remarkable degree of accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption

Nasal challenge with serotonin in asymptomatic hay fever patients.

To study the nasal response to serotonin, 14 asymptomatic hay fever patients received intranasal serotonin in increasing doses. Itching and the number of sneezes were noted, and the amount of secretion was measured and assayed for substance P. Nasal airway resistance was recorded by active posterior rhinomanometry. Serotonin induced a dose-dependent increase in nasal itching, number of sneezes and secretion. Substance P was found in 41 of 42 secretions. The median concentration was 10.3 pmol/l (range 0-28.9), and increased parallel to increasing doses of serotonin (P less than 0.001).

Adult

Seasonal allergic rhinitis and depot injection of a corticosteroid. Evaluation of the efficacy of medication early and late in the season based on detailed symptom recording.

It was the aim of this investigation to study the efficacy of a corticosteroid given as a depot injection in seasonal allergic rhinitis, the efficacy profile with regard to specific symptoms, and whether the injection is best given early in the season or later at the peak of the pollen count. An injection of 80 mg methylprednisolone showed a marked effect on nasal blockage lasting more than 4 weeks, and a moderate effect on eye symptoms, while the effect on nasal hypersecretion and sneezing could not be demonstrated. It is concluded that systemic corticosteroids may be indicated in severe hay fever, when symptoms, especially blockage, occur in spite of other types of therapy. If the physician prefers to give the corticosteroid as a depot injection, it is preferably given in the first half of the season when the pollen count is increasing.

Adolescent