Biomedical subjects
F Horak
Publications and source records attributed to F Horak.
Rhinoresistometry versus rhinomanometry--an evaluation.
Allergic nasal hyperreactivity is a common problem and many patients suffer from daily symptoms. Rhinomanometry is so far the only well established clinical method for objective assessment of nasal patency, although several expressions of nasal patency have been reported. Universal standardisation was achieved in 1983 in Brussels by Clement et al. [1], but many specialists are looking for a system giving more information on the functional aspects of the nose. A new development arising from active anterior rhinomanometry is rhinoresistometry. We tested this equipment, which has been introduced with new software for calculation and graphic presentation. 24 adult volunteers with proven allergy to grass pollen were examined immediately after long-term challenge in the Vienna Challenge Chamber [3] and 15 minutes after decongestion by application of 5% ephedrine solution. The similarity and differences between rhinomanometry and rhinoresistometry, as well as the value of the additional parameters are pointed out. Our data indicate that rhinoresistometry is a rapid, reproducible and non-invasive technique, which gives extended information in comparison to classic rhinomanometry. The results correlate very well with the findings obtained by the standard method. This pilot study demonstrates the benefit of the new parameters.
Identification of common allergenic structures in mugwort and ragweed pollen.
UNLABELLED: Identification of common allergenic structures in mugwort and ragweed pollen. BACKGROUND: Despite the rare occurrence of ragweed in Middle Europe, a surprisingly high number of patients allergic to mugwort, a frequently encountered weed, display IgE reactivity against ragweed pollen allergens. OBJECTIVE: The aim of this study was to investigate whether the high prevalence of IgE reactivity against ragweed in patients allergic to mugwort is caused by the presence of common allergenic determinants. We also sought to characterize any cross-reactive allergens. METHODS: Common allergenic structures in mugwort and ragweed pollen were characterized by qualitative IgE immunoblot inhibition experiments performed with natural allergen extracts and recombinant allergens. The degree of cross-reactivity was estimated by quantitative CAP-FEIA competitions. The clinical significance of cross-reactive IgE antibodies was studied with histamine release experiments and nasal provocation tests. RESULTS: Mugwort and ragweed RAST values were significantly correlated in a population of 82 Austrian patients allergic to mugwort. IgE antibodies cross-reacted with allergens of comparable molecular weight that were present in both extracts. By using recombinant birch profilin and specific antisera for IgE inhibition experiments, profilin was identified as one of the cross-reactive components in mugwort and ragweed pollen. Preincubation of sera from patients allergic to mugwort with mugwort extract inhibited IgE binding to ragweed pollen extract greater than 80%. Mugwort and ragweed pollen extract induced comparable histamine release and reduction of nasal air flow in a patient with IgE reactivity against the major mugwort allergen Art v 1. CONCLUSION: In addition to profilin, mugwort and ragweed pollen contain a number of cross-reactive allergens, among them the major mugwort allergen Art v 1. Cross-reactive IgE antibodies can lead to clinically significant allergic reactions.
Effect of continuous allergen challenge on clinical symptoms and mediator release in dust-mite-allergic patients.
This study investigated the early, prolonged immediate, and late-phase reactions of dust-mite-sensitive subjects undergoing long-term challenge in the Vienna challenge chamber (VCC) in terms of clinical symptoms and inflammatory mediator level patterns in nasal lavage fluids. A concentration of 70 ng Der p 1/m3 of air (feces of Dermatophagoides) was maintained over 8 h in the VCC. To show the clinical impact of this challenge model, the effect of a histamine H1-receptor antagonist that also has some antiallergic properties (loratadine) was also investigated. The study followed a double-blind, placebo-controlled, crossover design. Medication was given orally over 7 days before the provocation at a dose of 10 mg once daily. All 12 patients, whose dust-mite sensitivity was confirmed by disease history, skin prick test, and RAST, completed the challenge session. The documentation of the chosen parameters was performed every 30 min. Subjective nasal and ocular symptoms were assessed via a visual analog scale of 100 mm, nasal flow was recorded by active anterior rhinomanometry, and mediator release was evaluated with nasal lavages. Clinical aspect: the whole sample population showed a rise of nasal and ocular symptom severity and a nasal flow reduction, which were perceptibly, but not significantly attenuated by active drug treatment. Mediator pattern: in each patient, prostaglandin (PG)D2 and leukotriene (LT)C4 levels peaked within the first 2 h of provocation, PGD2 then moving toward baseline levels, and LTC4 then again rising continuously. Eosinophil cationic protein (ECP) exhibited a constant level increase over the whole provocation period, and tryptase levels did not change significantly. Whereas the area under the curve values of tryptase and ECP were higher in drug-treated patients than the placebo group, the early PGD2 peak occurring during the first two challenge hours seemed to be mitigated by loratadine. These results reveal that there is no link between the clinical symptoms, the drug efficacy, and the released mediators (LTC4, PGD2, ECP, and tryptase).
Environmental priming influences allergen-specific nasal reactivity.
BACKGROUND: Preceding mucosal response to one allergen leads to the priming of the nasal mucosal response to another allergen. This study aimed to determine whether environmental allergens, especially ubiquitous animal dander, can induce nasal priming. METHODS: We investigated 26 grass-pollen-allergic subjects with additional sensitization to other aeroallergens. We performed continuous allergen challenge for 2 h with 1500 Dactylis glomerata pollen/m3 in the Vienna challenge chamber. The nasal flow at 150 Pa was examined, and subjective scores were obtained every 15 min. Statistical analysis was calculated from the area under curve of nasal flow reduction by Student's t-test and the Mann-Whitney U-test. Alpha was 0.05. RESULTS: In subjects with positive cat-dander RAST (class of > or = 3), besides grass-pollen allergy, the specific nasal allergic reaction to Dactylis challenge was significantly pronounced (P < 0.01), and an earlier onset of reaction was evident. The same results were obtained with additional sensitization to dog dander (P < 0.05). Concomitant sensitization to mugwort also led to escalating symptoms (P < 0.05). CONCLUSIONS: These results indicate that a specific nasal allergic reaction is augmented by environmental priming caused by ubiquitous animal dander and possibly is influenced by the daily use of spices.
Efficacy and safety relative to placebo of an oral formulation of cetirizine and sustained-release pseudoephedrine in the management of nasal congestion.
BACKGROUND: The aim of this study was to assess the clinical efficacy of an oral formulation of cetirizine 5 mg with sustained-release pseudoephedrine (PSE) 120 mg relative to placebo in patients with nasal congestion. METHODS: Twenty-four patients with perennial rhinitis due to house-dust-mite (HDM) allergy were recruited in this crossover study. A treatment period of 1 week, in which cetirizine/PSE was administered twice daily, was followed by a washout period of at least 2 weeks and a further period of 1 week in which the alternative treatment was given to each patient. Immediately after the first dose of each medication (day 1), nasal congestion and related symptoms were assessed during a 7-h challenge with HDM feces, with the Vienna Challenge Chamber (VCC), to investigate onset of action of the preparation. A second challenge of 3-h duration, carried out at least 12 h after the final dose, was undertaken after 1 week (mean) of twice-daily treatment to assess residual effects of the formulation after achievement of steady state. RESULTS: The oral formulation of cetirizine/PSE was significantly (P<0.001) superior to placebo in improving nasal obstruction during both challenges. The improvement in nasal airflow and nasal patency was significantly greater with cetirizine/PSE than with placebo (P<0.02). In addition, subjective assessment of nasal symptoms showed that cetirizine/PSE was significantly superior to placebo in both challenges for the sum of nasal obstruction scores (P<0.01). Both medications were well tolerated, and no serious adverse events occurred during the study. CONCLUSIONS: In this study, cetirizine/PSE relieved nasal congestion and other objective and subjective symptoms to a significantly greater extent than placebo. No serious adverse events occurred, and both regimens were equally well tolerated.
[Protective effect of acupuncture on allergen provoked rhinitis].
A study of the protective effect of an acupuncture therapy against a nasal allergen-provoked rhinitis was undertaken on patients suffering from seasonal allergic rhinitis. The effects of a specific acupuncture therapy ("verum") were compared with those of a non-specific acupuncture therapy ("placebo"). The allergen-provocation was carried out in the "Vienna Provocation Chamber" (VCC) (Horak, 1987). 24 patients suffering from seasonal allergic rhinitis were allocated at random either to Group B and given a specific ("verum") acupuncture therapy or to Group A and given a non-specific ("placebo") acupuncture therapy. A nasal allergen-provocation was carried out before onset and after completion of 9 treatments. The objective and subjective results of the allergen-provocation in the VCC were not able to verify a protective effect of the acupuncture therapy. The "Diary of Complaints (Symptoms)" which the participants had to keep over the 2 months following the treatment showed a definite reduction of the subjective complaints in the verum group during the second month. The range of scatter was too great for a statistically significant result.
Dose-dependent protection by azelastine eye drops against pollen-induced allergic conjunctivitis. A double-blind, placebo-controlled study.
The efficacy and tolerability of azelastine (CAS 58581-89-8) eye drops at three different doses (0.025%, 0.05% and 0.1%) were investigated in a double-blind, randomized, placebo-controlled, crossover study in 24 subjects with a history of allergic conjunctivitis/rhinoconjunctivitis, who were challenged, out of season, by airbone allergen in the "Vienna Challenge Chamber" (VCC). Subjects received a single dose of azelastine eye drops 60 min before the start of a 4 h challenge in the VCC. Additional local challenge, mimicking a gust of wind, was administered 15 min before the end of the session. Each of the 4 study days was separated by a 2 week washout period. Azelastine eye drops showed a dose-dependent inhibition of the development of itching of the eyes. The effect was most pronounced 15 min after the additional local challenge. A maximal effect was achieved at a dose of 0.05%. Similar effects were observed on lacrimation. Azelastine eye drops also dose-dependently inhibited the degree of conjunctival redness, measured by digital imaging, and tended to reduce the low incidence of chemosis observed. Ranking of the results of all symptoms for each treatment group confirmed the optimal effect at a dose of 0.05%. Azelastine eye drops had no effect on nasal and bronchial symptoms or on measurements of airways function (FEV1). No adverse effects of the treatments were reported. The data support the use of 0.05% azelastine eye drops in the treatment of allergic conjunctivitis/rhinoconjunctivitis.
Quantification of conjunctival vascular reaction by digital imaging.
BACKGROUND: No objective evaluation of the conjunctival provocation test (CPT) was possible until now. OBJECTIVE: The aim of this study was to develop a tool that would enable us to monitor conjunctival allergic inflammation by objective measurements. METHODS: Twenty-four patients allergic to grass pollen were challenged by a CPT with grass pollen and genuine grass pollen in the "Vienna Challenge Chamber." Patients were randomized to treatment with placebo or topical application of an H1-receptor antagonist (azelastine). Vascular reaction of the conjunctiva was repeatedly monitored by special video equipment. The signal was sent to a digital frame grabber, and digital image analysis was done with the aid of the WCUE-3 program (Olympus Optical Co., Hamburg, Germany). RESULTS: The CPT led to an immediate increase of the red density. This extension was linear within the first 15 minutes. During the long-term challenge, the increasing vascular effect lasted 2 hours. During active treatment a consistent reaction pattern was obvious; however, the corresponding levels were statistically lower (p = 0.022). CONCLUSION: The calculation of red density of the conjunctiva by digital analysis proved to be a sensitive tool for measuring the conjunctival allergic reaction. It is possible to overcome the insufficient subjective evaluation of the CPT by objective measurements of the vascular reaction.
The clinical safety of H1-receptor antagonists. An EAACI position paper.
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Influence of instruction, prediction, and afferent sensory information on the postural organization of step initiation.
1. Our previous study showed that two distinct postural modifications occurred when subjects were instructed to step, rather than maintain stance, in response to a backward surface translation: 1) the automatic postural responses to the surfaces perturbation were reduced in magnitude and 2) the anticipatory postural adjustments promoting foot-off were shortened in duration. This study investigates the extent to which task instruction, prediction of perturbation velocity, and afferent sensory information related to perturbation velocity are responsible for these postural modification. 2. Eleven human subjects were instructed in advance, to either maintain stance or step forward in response to a backward surface translation. Four different velocities of translation were used to perturb equilibrium. To assess the influence of predicted versus actual velocity information, the surface translations were presented in both a blocked order of increasing perturbation velocity (predictable) and a random order (unpredictable). Lower-extremity electromyographs (EMGs), ground reaction forces, and movement kinematics were quantified for both the automatic postural responses to perturbation and the anticipatory postural adjustments for step initiation. 3. The instruction to step was not solely responsible for the suppression of the automatic postural response. Prediction of perturbation velocity was required for significant suppression of the early automatic postural response when subjects stepped in response to the perturbation. When compared with the stance condition, the magnitude of the initial 50 ms of the automatic response in bilateral soleus and the left limb gastrocnemius (initial stance limb) was significantly reduced only when the perturbation velocities were presented in a blocked order. The magnitude of the automatic response was not reduced in the gastrocnemius of the right limb, which was always the initial swing limb and recruited for heel-off in the step conditions. This asymmetrical reduction of the gastrocnemius suggests that modification of the response was specific to the instruction, rather than a general decrease in the extensor muscle excitability. 4. The suppression of the early automatic postural response involved a change in the bias of the response. Despite the reduced magnitude during the predictable velocity step condition, the slope (i.e., gain) of the response with increasing velocities was not different from that of the stance condition. Thus the excitability of the automatic response was reduced by a relatively constant amount for each velocity when the perturbation velocity was predictable. 5. In contrast to the importance of velocity prediction for modification of the automatic postural response, actual velocity information was used for modification of the anticipatory postural adjustments when step was initiated in response to the surface perturbation. Regardless of whether the perturbation velocities were presented in a blocked or random order, the anticipatory postural adjustments were rapidly initiated and the duration of the postural adjustments for step initiation was shortened as the velocity of perturbation increased. 6. We conclude that the CNS uses prediction of perturbation velocity to modify the excitability of early automatic postural responses when the postural goal changes. In contrast, actual afferent velocity information can be used to modify the duration of the anticipatory postural adjustments for a voluntary step in response to perturbation. Thus the CNS utilizes feed-forward prediction to modify peripherally triggered postural responses, and utilizes immediate afferent information to modify the centrally initiated postural adjustments associated with voluntary movement.
Efficacy and tolerability of astemizole-D and Loratadine-D during prolonged, controlled allergen challenge in the Vienna Challenge Chamber.
This randomized, double-blind, single-dummy, cross-over trial was initiated to compare the efficacy and tolerability of once-daily astemizole-D (CAS 141623-30-5; 10 mg astemizole/240 mg pseudoephedrine) with twice-daily loratadine D (CAS 132316-36-0; 5 mg loratadine/120 mg pseudoephedrine) during prolonged, controlled allergen challenge in the Vienna Challenge Chamber. Twelve atopic patients participated in this study with a treatment duration of 3 days. Pollen challenges were made on days 1 and 3: the first to assess onset of drug action; the second to determine duration of drug effect. Drug efficacy was assessed using a number of standard objective and subjective measures. Onset of action was found to be generally comparable in both treatment groups for all parameters tested with a mean overall onset of action of 65 min during treatment with astemizole-D compared with 70 min on loratadine-D. As expected, astemizole-D tended to have a longer duration of action, with symptom severity lower with this agent than with loratadine-D during the second challenge session despite the differences in dosing schedule. However, inter-group differences did not attain statistical significance. Patient evaluations of therapeutic efficacy confirm these findings. Both drugs were well-tolerated, although a non-significant trend towards greater sleep impairment was seen during treatment with loratadine-D. In conclusion, astemizole-D was shown to be at least as effective and well tolerated as loratadine-D for the treatment of allergen-induced rhinoconjunctivitis during prolonged, controlled allergen challenge.
Efficacy of intranasally applied dimethindene maleate solution as spray in adult volunteers with symptoms of seasonal allergic rhinitis in the Vienna challenge chamber.
Twelve asymptomatic subjects (4 female, 8 male), being allergic to grass pollen proved by positive anamnesis, positive Prick-test and positive nasal provocation test, were challenged under controlled conditions with purified airborne grass pollen of Dactylis glomerata in the Vienna Challenge Chamber (VCC), located at the Universitätsklinik für Hals-Nasen-Ohrenheilkunde, Allgemeines Krankenhaus (AKH), der Stadt Wien, Vienna (Austria) by means of a double-blind, randomised, cross-over design, with 2 weeks wash-out periods between. Efficacy and safety of 2 concentrations of dimethindene (dimethindene maleate; DMM, CAS 3614-69-5, Fenistil resp. Foristal) 0.025% DMM, 0.1% DMM) were tested vs placebo as negative control and vs 0.1% azelastine as positive control, as topical nasal sprays. The tested nasal sprays were applied as single doses in the morning (2 puffs = 0.28 ml of the respective solution) to each nostril 15 min before the start of the 4 h lasting provocation procedure in the VCC, thus representing a total daily dose of 0.14 mg resp. 0.56 mg DMM and 0.56 mg azelastine, respectively. Compared to placebo, the objective variables nasal flow (150 Pa., measured by active anterior rhinomanometry) and nasal secretion (g), showed similar onset of antiobstructive and antisecretory effects in the nose after 0.1% DMM and 0.1% azelastine, respectively. The same applied for the subjective nasal symptom complex and for nasal symptom scores, evaluated by Visual Analog Scale (VAS): Time curves showed statistically significant and clinically relevant superiority of 0.1% DMM and 0.1% azelastine vs placebo, during the 4 h lasting provocation period. 0.025% DMM was not significantly different from placebo. No systemic adverse events were reported after the 4 tested preparations. Only a total of 3 subjects reported very slight local irritations (1 subject after placebo, 1 subject after 0.025% DMM and 1 subject after 0.1% azelastine). However, after 0.1% DMM no local adverse events were reported. It is concluded from this study that 0.1% DMM as nasal spray, is an efficient and safe galenical formulation for nasal spray application for patients suffering from seasonal allergic rhinitis (SAR).
Levodopa reduces muscle tone and lower extremity tremor in Parkinson's disease.
OBJECTIVE: We have quantified the effects of levodopa treatment in Parkinsonian subjects during maintained stance. METHODS: Electromyographic muscle activity during quiet stance was assessed in subjects with Parkinson's disease, who exhibited a fluctuating response to levodopa, and in age-matched control subjects. Stance stability was also assessed from mean displacement and velocity of the center of pressure excursions during stance. RESULTS: Lower extremity and trunk muscles showed high amplitude activity in all Parkinson's subjects when "off", and a 4-5 Hz tremor in three of these subjects. When "on", the amplitude of muscle activity was reduced in the distal muscles more than the proximal, while tremor was suppressed in all muscles. Corresponding to the excessive muscle activity, the Parkinson's subjects had increased velocity and variability of velocity in the anterior-posterior center of foot pressure excursions, but the mean displacement of the center of pressure excursion was not different from the controls. The velocity of center of pressure excursions in the Parkinson's subjects "on", approached those of the control subjects suggesting that the excessive distal muscle amplitude and tremor contributed to the high velocity of the center of pressure. CONCLUSIONS: These findings suggest that dopaminergic systems are involved in the regulation of muscle tone during stance. Depletion of dopaminergic transmission results in increased muscle tone and tremor in the lower extremities which may contribute to changes in posture and stability.
Oral antihistamine/decongestant treatment compared with intranasal corticosteroids in seasonal allergic rhinitis.
This international, multicentre, randomized, double-blind, double-dummy, parallel-group trial was undertaken to compare the efficacy and tolerability of once-daily astemizole-D (10 mg astemizole plus 240 mg pseudoephedrine) with beclomethasone nasal spray (0.05 mg/ml) two puffs/nostril administered twice daily in a total of 204 patients with seasonal allergic rhinitis. Treatment duration was 4 weeks. Although investigator assessments of symptom severity were generally comparable in the two treatment groups throughout the trial, statistically significant differences in favour of astemizole-D for sneezing and ocular symptoms were apparent at the end of the 4-week treatment period (P < 0.05). Patient diary data support these findings, with significant differences in favour of the antihistamine/decongestant combination reported for ocular symptoms after 2 weeks of treatment (P < 0.05) and non-significant trends for sneezing after 2 weeks and ocular symptoms over the entire treatment period (P = 0.07). Use of rescue medication for ocular symptoms was also significantly lower in the astemizole-D treatment group (P < 0.05). A wide range of adverse experiences were reported, however, there were no statistically significant differences in the type or incidence of those between the two treatment groups. In conclusion, astemizole-D appears to be at least as effective and well tolerated as intranasal beclomethasone in the treatment of seasonal allergic rhinitis, providing at least comparable relief from all nasal symptoms including congestion and significantly greater relief from ocular symptoms than the topical steroid.
Nasal function and bronchial hyperresponsiveness to methacholine in children.
The objective of the present study was to investigate nasal function by active anterior rhinomanometry with respect to spirometric data and bronchial hyperresponsiveness to methacholine in 9-year-old children. The study population consisted of 300 children (ages 8 to 11 years; mean, 9.3 years; 161 male, 139 female), who underwent basal rhinomanometry followed by a decongestion test and a lung function test consisting of spirometry and a methacholine provocation test. The flow values of the basal rhinomanometry showed a significant correlation with height and bronchial hyperresponsiveness. The consecutive decongestion test showed a marked increase in flow rates at each level, which was found to be significantly higher in children with bronchial hyperresponsiveness (p < 0.01). The spirometric data showed no influence on rhinomanometric values. These results suggest that nasal dysfunction and reactivity in terms of the decongestion test may be associated with bronchial hyperresponsiveness in children.
[Clinical study of the effectiveness of filters in vacuum cleaners for reducing the concentration of dust mites in the household].
The faeces of the dust mite are the most significant source of allergy for those allergic to the dust mite. During vacuum cleaning, faecal particles are emitted from the cleaner and into the air to form pathological concentrations. The aim of the study was to discover if these extreme concentrations could be prevented by the use of appropriate filters. As the allergen source, dust mite faeces were used. A Miele vacuum cleaner type S424i was used without filter, with S-Class filter, and with Super Air Clean Filter. In the first test 1 g, and in the second test 2 g of dust mite faecal particles were evenly spread and then vacumed up. While using each filter in turn, the expelled air was measured for faecal concentrations. The analysis was performed by counting the number of faecal particles, and determining the content of major allergen Der p I in the expelled air. Without a filter there was a massive concentration of faecal particles in the expelled air. The simple filter Type (S-class-filter) achieved a significant reduction on the emission of allergens. The more complex special filter (Super air clean filter), was able to remove all traces of allergens from the expelled air.
Controlled exposure to mite allergen for a dose-finding of dimethindene maleate (DMM).
The aim of the study was to develop a laboratory system to challenge mite allergic patients with physiological concentrations of Der p I in order to evaluate the efficacy of antiallergic drugs in mite allergic patients. A double-blind, placebo-controlled, cross-over study was designed with three consecutive sessions. Twelve patients with proven sensitivity to dust mite were treated with a single dose of dimethindene maleate in a FOAD formulation (4 and 8 mg vs. placebo) 12 h before a long-term challenge with mite allergen Der p I in the Vienna challenge chamber. Challenge was performed with a constant concentration of 40 ng Der p I per cubic meter of air for 4 h. Nasal parameters were recorded at 15 min intervals during long-term challenge. In comparison to placebo, dimethindene leads to a statistically significant reduction (p < 0.05) of the nasal response at both concentrations tested. The house-dust mite model in the Vienna challenge chamber thus proved to be a useful tool for drug investigations in mite allergies.