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Biomedical subjects

L Klimek

Publications and source records attributed to L Klimek.

At least 19 recordsLinked to original sources
PubMed2001

Prostaglandin E2 activates the ciliary beat frequency of cultured human nasal mucosa via the second messenger cyclic adenosine monophosphate.

Prostaglandins influence the ciliary beat frequency (CBF) of ciliated nasal epithelial cells and a stimulatory effect has been described for prostaglandin E2 (PGE2). Until now, it is not known whether PGE2 has direct ciliostimulatory properties or acts through a second messenger. In this study we investigated whether cyclic adenosine monophosphate (cAMP) is implicated in the signal transduction pathway of PGE2-induced activation of CBF. Ciliated cells of the nasal mucosa were cultured for up to 5 days whereafter the culture medium was removed and the cells were incubated with different concentrations of test solutions. The ciliated cells were recorded under a phase-contrast microscope and viewed in slow motion to count the frequency. PGE2 led to a dose-dependent increase in CBF. This became significant at concentrations of 10(-10) and 10(-5) M (P < 0.01) but not at 10(-13) M (P > 0.05). Addition of cAMP (10(-10) to 10(-5) M) caused a significant (P < 0.01) increase in CBF, whereas depletion of endogenous cAMP after pre-incubation with the adenylate cyclase activator forskolin (10(-5) M) prevented the PGE2-induced increase in CBF (P > 0.05). The ciliostimulatory effect of PGE2 depends on an intact functioning of adenylate cyclase. These results point out that cAMP is directly implicated in the signal transduction pathway of PGE2-induced stimulation of CBF in cultured human ciliated cells of the nasal mucosa.

Adult↗
PubMed2001

Generic or disease-specific quality of life scales to characterize health status in allergic rhinitis?

BACKGROUND: In patients with allergic rhinitis (AR), various instruments have been validated for the measurement of quality of life (QOL), which may be greatly reduced. However, it is not clear which QOL instruments should be used for the different types of AR and whether they are sensitive to treatment. METHODS: The QOL of patients suffering from symptomatic seasonal AR (sSAR) (before and during treatment with a topical or systemic antihistamine), symptomatic perennial AR (sPAR), and asymptomatic seasonal AR (aSAR) was determined with the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) as disease specific and with the Munich Life Dimension List (MLDL) and the Visual Analogue Scale for Quality of Life (VAS-QOL) as generic QOL instruments. RESULTS: The different forms of AR were associated with typical QOL patterns. In sSAR, we found severe limitation of the global QOL, reduced global life satisfaction, high ranking of practical problems, high limitation of activity, and a high degree of disturbance in all subscales of the RQLQ. In sPAR, there were moderate limitation of the global QOL, normal global life satisfaction, high ranking of practical problems, moderate limitation of activity, and a high degree of disturbance by common symptoms. Under antihistamine treatment, both systemic and nasal, a significant improvement of QOL parameters was found, reaching the levels of patients with aSAR after 2 weeks. CONCLUSION: QOL instruments can distinguish the impairment resulting from sSAR from that of sPAR and are sensitive to treatment with topical and systemic antihistamines. However, as the RQLQ was not designed to measure the short-term variations of disease status that appear in SAR, it may not demonstrate the rapid improvement of QOL under antihistamine treatment.

Adult↗
PubMed2001

[Allergen immunotherapy - a position paper of the German society for allergology and clinical immunology].

Mechanisms of allergen immunotherapy (AIT) are complex inducing numerous immunological effects. Successful AIT is most likely based on a functional switch of and tolerance induction in specific T cells downregulating allergic hypersensitivity and inflammation. Subcutaneous AIT for allergic rhinoconjunctivitis and allergic asthma has been successfully assessed in controlled studies with several clinically important allergens (i. e. birch-, grass- and mugwortpollen, dust mites, animal dander) and has shown convincing clinical efficacy. Considered as the only causal treatment besides allergen avoidance at present, AIT can alter the natural course of allergic diseases. Hymenopteravenom hypersensitivity (to bee- and wasp venom) treated with AIT gives the best results compared to AIT with other allergens. AIT is indicated in patients with IgE-mediated sensitizations and corresponding clinical symptoms to allergens, which do not or hardly permit allergen avoidance and which are available as suitable extracts. Decisions about indication and allergen selection should only be made by a physician with certified training or qualified knowledge and skills in allergology. AIT is administered by physicians experienced in this therapy. After addressing tolerability and present status of health the recommended or individually adjusted does is injected and precisely documented, followed by a mandatory waiting period of 30 minutes. Indication for and application of AIT in children are quite similar compared to the treatment of adults. Children tolerate AIT very well and benefit especially from its immunomodulatory effects. Risk factors for and results of unwanted systemic effects can effectively be minimized by training of the staff members involved, adhering to safety standards and immediate emergency treatment. Modified allergens, recombinant proteins and immunomodulatory adjuvants created by basic research are promises for an improved efficacy of AIT with reduced unwanted effects in the future.

Allergens↗
PubMed2000

Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds.

"Sniffin' Sticks" is a test of nasal chemosensory performance that is based on penlike odor-dispensing devices. It is comprised of three tests of olfactory function: tests for odor threshold, discrimination and identification. Previous work has already established its test-retest reliability and validity in comparison to established measures of olfactory sensitivity. The results of this test are presented as a composite TDI score--i.e., the sum of results obtained for threshold, discrimination and identification measures. The present multicenter investigation aimed at providing normative values in relation to different age groups. To this end, 966 patients were investigated in 11 centers. An additional study tried to establish values for the identification of anosmic patients, with 70 anosmics investigated in five specialized centers where the presence of anosmia was confirmed by means of olfactory evoked potentials. For healthy subjects, the TDI score at the 10th percentile was 24.5 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 28.8 for ages from 36 to 55 years and 27.5 for subjects older than 55 years. While these data can be used to estimate individual olfactory abilities in relation to a subject's age, hyposmia was defined as the 10th percentile score of 16- to 35-year-old subjects. Our latter study revealed that none of 70 anosmics reached a TDI score higher than 15. This score of 15 is regarded as the cut-off value for functional anosmia. These results provide the basis for the routine clinical evaluation of patients with olfactory disorders using "Sniffin' Sticks."

Adolescent↗
PubMed1999

A new method for the placement of brachytherapy probes in paranasal sinus and nasopharynx neoplasms.

PURPOSE: In afterloading therapy, the exact placement of the applicator is crucial for the result of radiotherapy. A deviation of few millimeters from the target leads to a significant reduction of radiation energy to the tumor. METHODS AND MATERIALS: We present a new method using a computer-assisted device for three-dimensional placing of afterloading probes based on CT scans that allows for the exact placement. RESULTS: Target points have been reached with an accuracy of 0.6 mm. Since 1991 we have used this technique for 24 clinical applications in 11 patients with recurrent neoplasms in the region of the paranasal sinuses and nasopharynx for palliative treatment. CONCLUSIONS: The presented method is a reliable and precise procedure for the positioning of afterloading probes, avoiding the inaccuracy of the traditional methods.

Adult↗
PubMed1999

Real-time simulation of tissue deformation for the nasal endoscopy simulator (NES).

Endonasal sinus surgery requires a great amount of training before it can be adequately performed. The complicated anatomy involved, the proximity of relevant structures, and the variability of the anatomy due to inborn or iatrogenic variations make several complications possible. Today, cadaver dissections are the "gold standard" for surgical training. To overcome the drawbacks of traditional training methods, the Fraunhofer Institute for Computer Graphics is currently developing a highly interactive medical simulation system for nasal endoscopy and endonasal sinus surgery, in cooperation with the Mainz University Hospital. For the simulation of a rhinoscopic procedure, not only are the realization of the 3D interaction and the geometric representation of the anatomical structures necessary, but also a real-time simulation of the deformation behavior constrained by the instrument collisions. The challenge is to close the gap between a maximal degree of realism and the required real-time conditions.

Cadaver↗
PubMed1999

[Specific immunotherapy (hyposensitization) in allergic rhinoconjunctivitis. Meta-analysis of effectiveness and side effects].

BACKGROUND: Specific immunotherapy (SIT) of allergic disorders as introduced by Freeman and Noon involves the application of gradually increasing doses of extracts of the material to which the individual is sensitive. SIT represents the only specific treatment that can be offered to allergic patients besides allergen avoidance. SIT has been widely used in patients with pollen allergic rhinitis and its clinical efficacy has been demonstrated in several controlled clinical trials. The underlying mechanism of this treatment is still not understood. Previous studies have focused on changes in serum antibodies, including blunting of seasonal rises in specific IgE and increases in specific IgG antibodies, especially of the IgG4 isotype. Recent studies have suggested an effect on T-lymphocytes, leading to a switch from a predominant Th2 response--that is, interleukin (IL)-4 and IL-5--to a Th1 response involving interferon (IFN)-gamma. The switch of a cytokine profile to a predominant IFN-gamma response results in inhibition of IL-4 dependent IgE production, which is reinforced by a decrease in the production of IL-4 by Th2 cells. METHODS: In the present study a meta-analysis was performed to evaluate all double-blind placebo-controlled studies investigating the effect of SIT on clinical and immunological treatment used in patients with allergic rhinoconjunctivitis. RESULTS: SIT was shown to be an effective treatment modality in allergic rhinoconjunctivitis, decreasing symptoms, the need for medication and reactivity in specific nasal and conjunctival provocation tests, as well as inflammatory markers. Histologically, a switch might be induced from a predominant Th2 cell profile to that of a Th1. CONCLUSIONS: In general, the efficacy of SIT is dependent on the allergen the individual patient is sensitive to, the quality and total amount of the allergen applied and the SIT schedule.

Conjunctivitis, Allergic↗
PubMed1999

The exposure of healthy volunteers to 200 ppm 1,1,1-trichloroethane increases the concentration of proinflammatory cytokines in nasal secretions.

OBJECTIVES: Irritating effects of organic solvents have usually been measured by means of questionnaires. The aim of the present study was to evaluate the sensitivity of different methods of detecting subclinical irritating effects. METHODS: Twelve healthy, non-smoking students were exposed to 200 ppm and to 20 ppm 1,1,1-trichloroethane in an exposure chamber, using a crossover design. The amounts of interleukins (IL)-1beta, IL-6 and IL-8 and prostaglandin E(2) (PGE(2)) in nasal secretions were measured. Mucociliary transport time was determined with the saccharine test. Ciliary beat frequency of nasal epithelial cells was measured with video-interference contrast microscopy. Subjective symptoms were assessed by questionnaire. RESULTS: Concentrations of ILs were significantly elevated after exposure to 200 ppm 1,1,1-trichloroethane (IL-1beta 82.4 vs. 28.8 pg/ml (medians), P=0.003; IL-6 12.2 vs. 7.2 pg/ml, P=0. 01; IL-8 549 vs. 424 pg/ml, P=0.007), whereas the other parameters remained unchanged. CONCLUSION: The interleukins measured proved to be sensitive indicators of irritating effects of 1,1, 1-trichloroethane. The German threshold limit (MAK value) of 200 ppm 1,1,1-trichloroethane does not prevent the subclinical inflammation of nasal mucosa.

Adult↗
PubMed1999

The effect of short-term immunotherapy with molecular standardized grass and rye allergens on eosinophil cationic protein and tryptase in nasal secretions.

BACKGROUND: Activation of mast cells and eosinophils under pollen exposure can be inhibited by specific immunotherapy. OBJECTIVE: The effect of short-term immunotherapy with 7 preseasonal injections of molecular standardized allergens from grass and rye pollen on eosinophil cationic protein (ECP) and tryptase levels in nasal secretions has been compared with symptomatic drug treatment in an open, randomized study with 48 patients. METHODS: Nasal reactivity and mediator levels in nasal secretions were measured at baseline, before season, in season, and after season. RESULTS: Symptom scores in the immunotherapy group were 134.5 (95% CI, 65 to 336) versus 386. 0 (95% CI, 185 to 563), significantly lower as in the drug-treated group. ECP and tryptase levels increased significantly during natural allergen exposition. The seasonal levels in the immunotherapy group were significantly lower than in the drug-treated group with 272.1 ng/mL (252.0 to 293.9 ng/mL; immunotherapy) versus 470.4 ng/mL (SEM, 435.6 to 508.0 ng/mL; drugs) for ECP and with 8.73 ng/mL (SEM, 8.20 to 9.29 ng/mL) versus 17.47 ng/mL (16.42 to 18.60 ng/mL) for tryptase (all, P <.001). The ECP level induced by nasal provocation was 105.6 ng/mL (99.0 to 112.6 ng/mL) versus 180.4 ng/mL (169.2 to 192.4 ng/mL), significantly lower (P <.001) in the immunotherapy group, as was the tryptase level with 12.12 ng/mL (11.53 to 12.75 ng/mL) versus 8.19 ng/mL (7. 79 to 8.62 ng/mL; P <.001) at the after-season visit. CONCLUSION: Short-term immunotherapy is able to reduce tryptase and ECP in nasal secretions more effectively than drug treatment in patients with allergic rhinitis.

Adolescent↗
PubMed1999

Norm values for eosinophil cationic protein in nasal secretions: influence of specimen collection.

BACKGROUND: Eosinophil granulocytes play an important role in allergic inflammation of the nasal mucosa. Eosinophil cationic protein (ECP) is a specific eosinophil granule protein released upon activation of these cells. ECP concentration in nasal secretions has been demonstrated to be a good marker for the activity of eosinophilic nasal mucosal inflammation. The clinical use of such a marker requires defined values which are regarded as pathological or within normal range. In analyses of nasal secretion samples, the sampling method has an important influence on the data obtained. OBJECTIVE: We investigated ECP levels in nasal secretions (NS) of healthy volunteers obtained by seven different methods of sample collection to define norm values and to evaluate the clinical use of the different methods. METHODS: A total of 839 healthy individuals were evaluated using blowing the nose (Bl: n = 82), suction (Suc: n = 69), Okuda microsuction technique (MSuc: n = 93), absorbent cotton wool samplers (CWS: n = 156), rubber-foam samplers (RFS: n = 193), nasal lavage (Lav: n = 112) and nasal spray washing (NSW: n = 134). RESULTS: Missing values occurred in more than 60% in Bl, Suc and MSuc, so that no norm range was defined for these methods. Norm range for ECP in NS was 5-46 ng/mL for CWS, 7-41 ng/mL for RFS, 4-51 ng/mL for NSW, and 3-31 ng/mL for Lav. CONCLUSIONS: When comparing seven different methods used in this study to collect nasal secretions and determine ECP levels, the method based upon absorption or nasal washing was the best.

Adolescent↗