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Biomedical subjects

J A Wihl

Publications and source records attributed to J A Wihl.

At least 19 recordsLinked to original sources

Systemic effects of two nasally administered glucocorticosteroids.

Two topical corticosteroids, budesonide (BUD) and beclomethasone dipropionate (BDP), both administered as suspensions in water, were investigated in healthy volunteers regarding influence on cortisol in plasma and urine (U-cortisol) after nasal application. In the first study, single doses of 200, 400, and 800 micrograms of BDP and BUD were given at 10:00 pm. In the second study, 100, 200, and 400 micrograms were given mornings and evenings for 4 days. In the single-dose study, none of the drugs or doses showed any significant influence on cortisol in plasma. However, U-cortisol decreased significantly after BUD 400 and 800 micrograms. In the multidose study, U-cortisol values were significantly reduced after all doses of BUD and the highest dose of BDP. The compounds tested showed different ability to cause measurable systemic effects after nasal application. The clinical implication is that the prescriber, when choosing a compound, should take the application site into consideration and should also be encouraged to find the lowest effective dose.

Administration, Intranasal

Contralateral differences among biomarkers determined by a modified nasal lavage technique after unilateral antigen challenge.

The concentration of biomarkers from vessels and inflammatory cells in nasal lavage fluid reflects the degree of hyperresponsiveness in patients with allergic rhinitis. The lavage has usually been performed of both nasal cavities together after prewashings and administration of decongestants. To improve the technique, we introduced a modification involving lavage of the nasal cavities separately without any prewashings or decongestants. We challenged 20 rhinitic subjects sensitive to timothy unilaterally with timothy extract. In nasal lavages performed before, immediately after, and 6 h after the challenge, we determined the concentrations of albumin, histamine, bradykinin, TAME (N-alpha-tosyl-L-arginine methyl ester)-esterase, and leukotriene C4 (LTC4). In eight subjects, the procedure was repeated 1 and 2 weeks later. After the challenge, albumin, bradykinin, TAME-esterase, and LTC4 in the nasal lavage fluid increased on the ipsilateral side but not on the contralateral side. Histamine did not increase after antigen challenge. After 6 h, the biomarkers were not increased. The concentrations of biomarkers did not differ between sides before the challenge and not between visits. Thus, the modified nasal lavage technique is reliable and improved compared to previous methods because it involves reproducible determinations of different biomarkers, and it is simple and easy to perform.

Adolescent

Specificity mapping of patients IgE response towards the tree pollen major allergens Aln g I, Bet v I and Cor a I.

The specificity pattern of IgE from non-treated tree pollen allergic patients (n = 38) were evaluated by solid phase absorption of serum samples followed by CRIE on alder, birch and hazel CIE precipitation profiles. The majority of the serum samples seemed to contain IgE antibodies with the following characteristics: specific towards Bet v I alone and common between Aln g I, Bet v I and/or Cor a I, 'II'. The IgE specificity profiles observed for 95% of the sera tested are compatible with birch pollen allergens being the only sensitizing allergens, indicating that the patients react to allergens from other tree pollens of the Fagales order due to IgE cross-reaction with the major allergens of birch and alder and/or hazel pollens.

Allergens

Immunotherapy of tree pollen allergy with a modified alginate conjugated birch pollen extract compared to an aluminium adsorbed extract.

The safety and efficacy of two birch pollen extracts, one chemically conjugated to alginate (Anjuvac) the other adsorbed to aluminium hydroxide (Alutard), were investigated in an open multicentre comparative study of 63 birch pollen allergic patients. Both extracts decreased the nasal symptoms during the birch pollen season. The changes in specific IgE and IgG were much the same in both treatment groups. The adverse reactions recorded were mild in both groups, but more frequent in the Anjuvac group, probably because of a more aggressive dose schedule though there were twice as many asthmatics in the Anjuvac group. The two investigated allergen extracts were useful alternatives for immunotherapy.

Adolescent

Secretory leukocyte protease inhibitor in normal, allergic and virus induced nasal secretions.

Secretory leukocyte protease inhibitor (SLPI) and alpha-1-proteinase inhibitor (alpha-1-PI), both inhibitors of granulocyte elastase, were studied in nasal secretions from healthy persons and from patients with allergic rhinitis and common cold. SLPI and granulocyte elastase were found in all samples, while alpha-1-PI was lacking in several. In all three groups SLPI was found in an active form and in excess of granulocyte elastase, which thus was completely inhibited. The results indicate that SLPI is the main inhibitor in nasal secretions and that alpha-1-PI plays a minor role.

Common Cold

Immunotherapy with partially purified and standardized tree pollen extracts. I. Clinical results from a three-year double-blind study of patients treated with pollen extracts either of birch or combinations of alder, birch and hazel.

Fifty-four adult patients with tree pollen-induced rhinitis (28), asthma (1), or rhinitis and asthma (25) were selected for immunotherapy with standardized and partly purified tree pollen extracts using a double blind protocol. The selection was based on clinical history, results of nasal or bronchial challenge, skin prick tests and RAST. Further, based on crossed radio-immunoelectrophoresis, sex, age and severity of symptoms, the patients were allocated in matched pairs and the treatment alternatives were randomly distributed within the pairs. Twenty-three patients treated with extracts composed of any combination of alder, birch and hazel pollen which matched their IgE response in CRIE (Group 1 (ABC)) and 22 patients receiving birch pollen extracts (Group 2 (B)) completed all 3 years of treatment. The in vivo results comprising symptom and medicine consumption scores are given here. Changes in specific skin and nasal reactivity as well as in immunological parameters are presented separately. No significant differences were demonstrated between the treatment groups in the two parameters. Both extracts were effective and reduced in general the symptom scores to one tenth of the starting level. Expressed another way, at the end of the study, the patients tolerated 30 times more pollen until symptoms of the same severity were elicited, compared to before. In the Nordic countries, spring-time asthma and rhino-conjunctivitis caused by pollen from deciduous trees can be effectively treated with an extract of birch pollen alone.

Adolescent

Immunotherapy with partially purified and standardized tree pollen extracts. II. Results of skin prick tests and nasal provocation tests from a three-year double-blind study of patients treated with pollen extracts either of birch or combinations of alder, birch and hazel.

Patients allergic to tree pollen entered a 3-year course of immunotherapy (1980-83) with either birch pollen extracts alone (n = 26) or patient-tailored extracts of birch, alder and hazel pollen (n = 27). The clinical and immunological results of this study are published elsewhere. This paper contains an evaluation of skin prick test and nasal provocation test results. There were no significant differences between the two treatment groups concerning these two parameters. In both groups the allergen-specific sensitivity in the skin showed seasonal variations but a significant decrease. During the years of treatment there was also a significant decrease in the specific sensitivity of the nasal mucosa. With the present demands for purification and standardization of allergen extracts it is of practical and economic interest to know that tree pollen-allergic patients showing positive reactions to birch, alder and hazel extracts can be effectively treated using birch pollen extract alone.

Asthma

Immunotherapy with partially purified and standardized tree pollen extracts. III. Specific IgE response to the major allergens of alder, birch and hazel pollen during immunotherapy.

Patients allergic to pollen from alder, birch and hazel were hyposensitized during a 3-year period with either birch pollen extract alone (n = 24) or a mixture of one or more of alder, birch and hazel pollen extracts (n = 27). The effect of the treatment was evaluated by RAST and tandem crossed-radioimmunoelectrophoresis (tandem-CRIE). The patient' specific IgE response to the major allergens of alder (Aln g I), birch (Bet v I) and hazel (Cor a I and Cor a II), as measured by tandem-CRIE, and the total specific IgE response, measured by RAST, decreased significantly (Pc less than 0.05) during immunotherapy, irrespective of the extract used during the treatment. There was no significant difference (Pc less than 0.05) between the two treatment groups. The results obtained indicate either that birch pollen extract alone is adequate in the treatment of the studied patient group or the patients had been sensitized towards birch pollen alone.

Clinical Trials as Topic

Rhinomanometry and nasal peak expiratory and inspiratory flow rate.

Variation in nasal patency can be studied by rhinomanometry as well as by nasal expiratory and inspiratory peak flow rate. The accuracy of 12 sets of peak flow meters was tested in a standardized way using a pump. Differences between flow meters were found. Consequently it is recommended for a patient to use the same flow meter throughout a study. Comparison between nasal expiratory and inspiratory peak flow was performed before and after provocation of 12 grass pollen-allergic patients. Inspiratory peak flow showed certain advantages compared with expiratory peak flow measurements. The results can best be expressed as the means rather than the top values of three consecutive registrations. Twelve healthy subjects were also tested with rhinomanometry, nasal expiratory and inspiratory peak flow before and after decongestion with nose spray. Comparisons among the three methods showed significant correlations.

Adult

Tree pollen allergy. III. Cross reactions based on results from skin prick tests and the RAST in hay fever patients. A multi-centre study.

872 adult hay fever patients were investigated with skin tests, using 20 different tree pollen allergens, and Phadebas RAST, using eight different tree pollen allergens. Correlation between test results with the different allergens were studied employing the Spearman's correlation coefficient (Rho). Most combinations showed statistically significant correlations. The highest values of Rho (0.8-0.9) were found for pollen from combinations of trees belonging to the families Betulaceae, Corylaceae and Fagaceae (birch, alder, hazel, beech and oak). High values were also found between pollens from aspen and sallow (belonging to Salicaceae). With several of the trees a high degree of pollen cross sensitization was found, even with trees from a different plant family. Since most of the patients were allergic to birch pollen, some of the reactions to other pollens could be due to allergens shared by birch. To exclude this possibility, a separate analysis was performed for patients having no birch pollen allergy. Even in these patients evidence of cross sensitization was found. It is concluded that cross reactions are common among tree pollens and are most pronounced within botanical families.

Adult

Flowers and other trigger factors in asthma and rhinitis--an inquiry study.

Six hundred and eighty adult patients with asthma and/or rhinitis were questioned about symptoms elicited by 46 different flowers and 10 common non-specific environmental trigger factors listed in a questionnaire. Flowers or birch twigs were reported to elicit symptoms in 79% of the patients, somewhat more often in rhinitis than in asthma patients, and caused symptoms as often in non-atopics as in atopics. Birch twig and marguerite most frequently induced symptoms, followed by strongly smelling flowers such as hyacinth, lilac, and lily of the valley. Unspecific irritants caused symptoms in 98% of the asthmatics and in 67% of patients with rhinitis. Tobacco smoke and perfumes were the most important troublemakers. A significant positive correlation was found for elicitation of symptoms from flowers and from certain non-specific irritants. It is concluded that non-specific hyperreactivity as well as reaginic hypersensitivity are the mechanisms involved when birch twigs and flowers elicit symptoms.

Adult

A manufacturer's criteria for in-house reference preparations for RAST inhibition.

Reagents employed for RAST-inhibition need careful characterization. An allergen reference preparation was produced from carefully selected raw materials. After immunochemical and biochemical characterization, the reference preparation was used to produce allergen reference paper disks. Their quality was controlled by the amount of bound protein and serum titration, which should yield an S-shaped dose-response curve and specific binding of IgE of at least ten times more than background binding. In parallel, the biologic activity of the allergen reference preparations was established in quantitative skin prick tests in at least 20 allergic patients. From these patients, serum samples were collected and pooled after careful characterization. All three necessary reagents for RAST-inhibition (extract, disks, and serum pool) were stabilized by freeze-drying. The reproducibility of the assay procedure itself was checked by documenting the 50% inhibition value of the reference preparation, accepting only values within +/- 2 SD. By employing such reagents we could measure the activity of alum-adsorbed grass pollen extracts with sufficient precision, ie, the coefficient of variation of the mean potency of 12 batches was less than 40%.

Allergens

Methodological aspects of nasal allergen challenges based on a three-year tree pollen immunotherapy study.

During 3 years of immunotherapy with tree pollen extracts, 31 patients were provoked annually. Changes in nasal reactivity were followed by registration of expiratory nasal peak flow, number of sneezes, and amount of secretion. The reproducibility of the peak flow measurements was studied. The results from all three parameters were used to form a total nasal provocation score which, better than each parameter separately, could demonstrate the variation in sensitivity. Provocation with an allergen concentration of 1 HEP was the most effective means of showing changes in specific sensitivity of nasal mucosa.

Administration, Inhalation