Endothelial cells and angiogenesis intensity in lung cancer.

We focused our studies on single endothelial cells (ECs) scattered in extracellular matrix in lung cancer tumors. Neovascularization was evaluated in 100 tumors obtained from patients operated for lung cancer, in relation to histological type, tumor differentiation and clinical stage of the disease. Angiogenic objects (single endothelial cells and microvessels) were identified by immunohistochemistry using monoclonal antibodies against von Willebrand factor. The count of angiogenic objects per 1 mm2 in each section was determined in a "hot spot" located at the margin of the tumor. We used an arbitrary scale of angiogenesis intensity: 1 - 0-200, 2 - 201-400, 3 - >400 angiogenic objects/mm2. A majority (57%) of the examined cases belonged to the group 2. The angiogenesis intensity measured by the single EC numbers/mm2 correlates with the histological type and the differentiation of the tumors. There was no such a correlation when the angiogenesis intensity was measured by counting total angiogenic objects (microvessels + EC) number/mm2. Single EC number/mm2 in different histological types of cancer were as follows: 162+/-121 in squamous cell (SqCC), 194+/-71 in adenocarcinoma (AdC), 225+/-145 in large cell (LCC), 264+/-52 in small cell (SCC), 279+/-173 in combined cancer. The differences between the EC counts in the different histological types of lung cancers were statistically significant in the following pairs: SqCC vs SCC (p=0.0233) and AdC vs SCC (p=0.0409). The correlation between EC count in the "hot spot" and the grade of tumor differentiation was statistically significant for G1 vs G4 (p=0.0007) and G1 vs G2 (p=0.0411). Our results suggest that higher numbers of EC/mm2 may confirm rapid development of angioneogenesis. These relations should be examined in larger series of cases.

[The effect of specific immunotherapy on bronchial hyperreactivity in patients with bronchial asthma]. / Wplyw immunoterapii swoistej na nadreaktywnosc oskrzeli u chorych na astme oskrzelowa.

The aim of the paper was to answer the question, weather specific immunotherapy affected bronchial hyperreactivity in asthmatic patients. The authors used their own results of specific immunotherapy studies and those found in the literature. From these data the following conclusions were formulated: 1. Specific immunotherapy decreases specific bronchial hyperreactivity. The improvement is seen both in the early and late asthmatic reactions. 2. No significant effects of specific immunotherapy on nonspecific bronchial hyperreactivity were found. 3. In order to find an unequivocal answer to the question above multicenter studies on a representative group of patients based on the same protocol and lasting for at least 5 years are necessary.

[The effect of local specific bronchial immunotherapy (LIT) on specific and non-specific bronchial hyperreactivity in patients with bronchial asthma sensitive to housedust mites]. / Wplyw dooskrzelowej immunoterapii swoistej (LIT) na swoista i nieswoista nadreaktywnosc oskrzeli u chorych na astme oskrzelowa uczulonych na roztocza kurzu domowego.

The aim of the study was to evaluate the effect of LIT with mite allergens given by dry powder inhalation on bronchial hyperreactivity after histamine and allergen inhalation in patients suffering from atopic mite asthma. The study was conducted in a group of 17 asthmatics (9 patients Hypoinhal Dermatophagoides, 8 patients placebo). A decrease in specific (early asthmatic reaction during specific bronchial provocation test) and non-specific bronchial hyperreactivity has been revealed in the group treated with Hypoinhal Dermatophagoides. No changes were observed in placebo group. A slight improvement in LAR (late asthmatic reaction during specific bronchial provocation test) was observed, but the results were not statistically significant.

[Expression of adhesion molecules LFA-1 (CD11a and ICAM-1 (CD54) on lymphocytes and chemokines IL-8 and MCP-1 concentrations in bronchoalveolar lavage of patients with asthma or chronic obstructive pulmonary disease]. / Ekspresja czasteczek adhezyjnych LFA-1 (CD11a) i ICAM-1 (CD54) na limfocytach oraz stezenia chemokin IL-8 i MCP-1 w materiale z plukania oskrzelowo-pecherzykowego u chorych na astme oskrzelowa i przewlekla obturacyjna chorobe pluc.

Chemokines and cellular adhesion molecules are crucial determinants of the migration of immune effector cells to the tissues asthma and chronic obstructive pulmonary disease (COPD) are a complex of conditions, which have airflow limitation in common. The aim of this study was to determine the numbers and percentages of lymphocytes expressing adhesion molecules: LFA-1, ICAM-1 together with assessment of chemokines concentrations: IL-8 and MCP-1 in bronchoalveolar lavage fluid (BAL) of patients with asthma or chronic obstructive pulmonary disease (COPD). 12 patients with asthma, 14 patients with COPD, and 6 subjects of control group took part in this study. The expression of LFA-1 and ICAM-1 was assessed on lymphocytes by using immunohistochemistry (streptavidyn-biotin, DAKO, Denmark). ELISA test was used to measure IL-8 and MCP-1 concentrations in BAL (kits from R&D, USA). The percentage of lymphocytes expressing LFA-1 and ICAM-1 were: 33.9 +/- 23.8% and 25.8 +/- 12.2% in COPD patients, 23.9 +/- 12.1% and 15.3 +/- 4.42% in asthma patients, and 14.2 +/- 10% and 5.2 +/- 1.6% in the control group respectively. There was observed significant difference between the percentage of lymphocytes expressing LFA-1 and ICAM-1 of COPD and the control group. The concentrations of IL-8 were: 2306 +/- 1501 pg/ml in COPD, 233 +/- 27.3 pg/ml in asthma and 64 +/- 28.7 in the control group (p < 0.05). The concentrations of MCP-1 were: 768.9 +/- 668.1 pg/ml in COPD, 126.8 +/- 30.8 pg/ml in asthma, and 83.0 +/- 16.4 pg/ml in the control group (p < 0.05). There was observed correlation between lymphocytes expressing LFA-1 and IL-8 concentration (r = +0.5, p < 0.05) and between lymphocytes expressing LFA-1 and MCP-1 concentration (r = +0.5, p < 0.05), and between lymphocytes expressing ICAM-1 and MCP-1 concentration (r = +0.4, p < 0.05) only in COPD patients. Our data suggest that LFA-1 and ICAM-1 are important molecules in the recruitment of leukocytes and together with IL-8 and MCP-1 may have a role in pathomechanism of inflammation in asthma and especially in COPD.

[Interleukin-13 in the nasal lavage of pollinosis patients after specific intranasal challenge]. / Interleukina-13 w popluczynach nosa chorych na pylkowice po swoistej prowokacji donosowej.

The unique properties of interleukin-13 have drawn the attention of investigators to its role in atopic diseases and in the mechanism of specific immunotherapy. The aim of this paper was to determine whether the presence of interleukin-13 will, apart from interleukina-4, be found in the nasal lavage after specific challenge and if the levels of these cytokines will differ. The studies included 13 patients in whom grass and rye pollen allergy was confirmed by the case history, skin tests and the presence of specific IgE in the blood serum. In all these persons active anterior rhinomanometry and than specific challenge with gradually increasing concentrations of the grass pollen allergen were performed before the season. At the end of these challenge, nasal lavage was done and the lavage fluid was preparated for determination of IL-4 and IL-13. Both cytokines were found to be present in the nasal lavage and in 6 patients the IL-13 concentration was higher than that of IL-4. Three of these patients had been previously hyposensitized. Although the results presented here are preliminary, they may provide inspiration four further investigations of the role of IL-13 in the specific immunotherapy in pollinosis patients.

[The effect of sputum induction on spirometry parameters in patients with bronchial asthma]. / Wplyw indukcji plwociny na parametry spirometryczne u chorych na astme oskrzelowa.

Evaluation of differential cell count and biochemical parameters in sputum seems to be a valuable method in asthma studies. The purpose of the paper was to evaluate the effects of sputum induction alone and after fenoterol and salmeterol premedication, on spirometry in asthma patients. The another aim of the study was to observe the correlation between bronchial hyperreactivity and decreases in FEV1 and MEF50 in asthmatics during sputum induction. The studies were carried out on 20 mild to moderate asthma patients (FEV1 baseline 79 +/- 16% of the predicted values) who inhaled an increasing concentration of hypertonic saline (3%, 4% and 5%), using an ultrasonic nebuliser. The forced expiratory volume in one second and MEF50, as the good indicators of bronchial obturation, were evaluated. During the sputum induction significant decreases in FEV1 and MEF50 were observed, which were proportional to the concentration of NaCl. After inhalation of 3% of NaCl the mean of FEV1 was 87.2 +/- 12.7% of the baseline, after 4%--84.3 +/- 16.9% and 5%--77.4 +/- 19.8%. No significant correlation between bronchial hyperreactivity and the induced decreases in FEV1 and MEF50 were found. Fenoterol and salmeterol fully prevented bronchial obturation during sputum induction.

[Evaluation of the enhaled glucocorticosteroid effect on non-specific and specific bronchial reactivity with particular reference to the late inflammatory phase in atopic asthma patients. I. The effect of a single dose of budesonide R on specific and non-specific bronchial reactivity]. / Wplyw wziewnych glikokortykosteroidów na nieswoista i poalergenowa reaktywnosc oskrzeli ze szczególnym uwzglednieniem póznej fazy zapalnej u chorych na atopowa astme oskrzelowa. I. Wplyw pojedynczej dawki budezonidu R na swoista i nieswoista reaktywnosc oskrzeli.

The effect of a single dose of 320 micrograms of budesonide R on specific and non-specific bronchial response was evaluated. The study was carried out on a group of 12 patients suffering from mild allergic asthma, sensitive to Dermatophagoides pteronyssinus (D. pteronyssinus). On the first day the bronchial provocation test (BPT) with metacholine was performed, and the next day the effect of a single dose of the drug studied on bronchial response to metacholine was evaluated. On the third day sBPT with D. pteronyssinus allergen was performed. The allergen challenge could induce an early (EAR) and a late asthmatic reaction (LAR). After the BPT with the allergen, a 42 days' run-out period was required to eliminate the effects of the allergen provocation on the results of the next tests. Before the evaluation of the effect of budesonide on the allergen challenge, the non-specific response to metacholine was checked again. The results indicate that a single dose of budesonide R does not affect non-specific and specific bronchial response.

[Evaluation of the inhaled glucocorticosteroid effects on non specific bronchial reactivity with particular reference to the late inflammatory phase in atopic asthma patients. II. The effect of regular administration of budesonide R on specific and non-specific bronchial reactivity]. / Wplyw wziewnych glikokortykosteroidów na nieswoista i poalergenowa reaktywnosc oskrzeli ze szczególnym uwzglednieniem póznej fazy zapalnej u chorych na atopowa astme oskrzelowa. II. Wplyw regularnego stosowania budezonidu R na odczyn zapalny oraz swoista i nieswoista reaktywnosc oskrzeli.

The purpose of the study was to determine whether regular administration of budesonide R decreases inflammation, specific and non-specific bronchial hyperreactivity in allergic asthma patients. The studies were carried out on 16 patients suffering from mild to moderate allergic asthma, sensitive to D. pteronyssinus allergen. After performance of the specific and non-specific bronchial provocation tests, collection of blood samples for an ECP evaluation, the patients were regularly treated with budesonide R, 2 x 320 micrograms for a period of 8 weeks. At the end of the study the BPTs and blood collection were repeated. BPTs with methacholine and D. pteronyssinus were performed according to Ryan's method. After the allergen challenge, early (EAR) and late asthmatic reaction (LAR) were to be observed. After the therapy non-specific BHR to methacholine expressed as PC20FEV1 and specific BHR to allergen (PD20FEV1D. pteronyssinus) and serum ECP concentrations decreased significantly. Although after the treatment with budesonide R, the patients had to inhale much larger amounts of allergen, in order to induce EAR, the number of LAR did not change significantly. After treatment the LAR appeared about 1 hour later and the decrease in FEV1 was less than previously. We conclude that budesonide R decreases the intensity of the inflammation and BHR.

[The efficacy of a new medication -- intranasal glucocorticoid mometasone furoate (Nasonex) -- in seasonal allergic rhinitis]. / Skutecznosc nowego preparatu steroidowego Nasonex-aerozol w leczeniu sezonowego, alergicznego niezytu nosa.

The aim of this open study was to evaluate the efficacy and safety of new topical corticosteroid Nasonex (mometasone furoate) in allergic, seasonal rhinitis. The investigations were carried out on 30 patients with proven grass pollen allergy. Nasonex was administered intranasally during the pollen season, in a single dose 200 micrograms. During the 3 subsequent visits nasal and nonnasal symptom (total and individual) scores and patient reaction to the treatment were evaluated. Rhinomanometry and number of eosinophils in nasal smear were calculated before and after the treatment. Complete or marked relief of symptoms was observed in 24 patients, moderate improvement in 4 patients and no positive reaction in 2 cases. Nasonex markedly inhibited eosinophil influx to the nasal mucosa. No adverse reaction was observed during 2-week Nasonex treatment. We conclude that Nasonex aerosol is a very effective and well tolerated drug in the treatment of seasonal allergic rhinitis.

[Clinical evaluation of 12 week salmeterol therapy in allergic asthma patients]. / Kliniczna ocena 12 tygodniowej terapii salmeterolem chorych na alergiczna astme oskrzelowa.

The purpose of the study was to evaluate the efficacy of salmeterol in asthma therapy. The study was performed on a group of 16 allergic asthma patients sensitive to house dust mite allergens. After a run-in period the patients were treated with salmeterol, 2 x 50 micrograms, for a period of 12 weeks. They noted an intensity of asthma symptoms, morning and evening PEF, beta 2-agonist consumption and adverse in their diary cards. On the visit to the clinic spirometry was performed. During the treatment a significant reduction in the symptom score, PEF variation, beta-agonist consumption and an increase in the value of morning and evening PEF were noted. The above results indicate the great efficacy of salmeterol in asthma therapy.

[An immunologic evaluation of Polish pollen extract Catalet "C" and Catalet "D" in patients with pollinosis]. / Immunologiczna ocena polskich preparatów alergenowych Catalet "C" i Catalet "D" u chorych na pylkowice.

In a group of 41 hay fever and/or seasonal asthma patients, sensitive to weed or tree pollens the influence of specific immunotherapy (sIT) on the level of IgE, specific IgE and IgG4, and HR induced by anti-IgE and specific allergens was evaluated. It was shown that both allergenic extracts, Catalet C and Catalet D, are really immunogenic, which is manifested in a decrease in specific IgE and in a marked increase in specific IgG4, after 2 years of sIT. In comparison with the placebo, the sensitivity of blood basophils to both specific allergens and non-specific factors significantly decreased.

[Clinical evaluation of Polish allergen extracts Catalet C and Catalet D in patients with pollinosis]. / Kliniczna ocena Polskich preparat-ow alergenowych Catalet C i Catalet D w leczeniu chorych na pylkowicle.

The aim of this paper was to evaluate the clinical efficacy, individual tolerance and side effects of allergen extracts, a weed pollen vaccine Catalet C and a tree pollen vaccine Catalet D. The study was carried out on a group of 41 patients aged from 15 to 46 years in comparison with a placebo group (36 patients). A good tolerance, no serious side effects and a high clinical efficacy, manifested in diminution of pollinosis symptoms in more than 80% of patients was noted. In the treated patients a significant reduction of antiallergic drug consumption in the pollen season was noted as compared with the placebo. The extracts Catalet C and Catalet D are usefull in the specific immunotherapy in weed and tree pollen allergic patients.

[Efficacy and tolerance of allergenic extracts Allergovit and Novo-Helisen depot in immunotherapy of allergic diseases]. / Skutecznosc i tolerancja preparatów alergenowych Allergovit i Novo-Helisen depot w immunoterapii chorób alergicznych.

The aim of this study was to evaluate the efficacy, tolerance and immunogenity of allergenic extracts: Allergovit and Novo-Hellisen depot (produced by Allergopharma--Germany), used for sIT in pollinosis and house dust mite allergy. The treatment was carried out on 40 patients for three years. The evaluation included the results of a physical examination, the score of symptoms from self-observations and the consumption of antiallergic medicines. In addition to the serum IgE and IgG4 the percentage of histamine, liberated by a-IgE and specific allergens, from peripheral blood basophils was determined. In some of patients treated with Novo-Helisen depot the specific and nonspecific bronchial challenge tests were made. It was shown that the allergenic extracts Allergovit and Novo-Helisen depot are effective in treatment of pollinosis and house dust mite allergy, and are well tolerated by the patients. The changes in humoral response during sIT manifest their immunogenity. The sIT with Allergovit decreases the sensitivity of the peripheral blood basophils, whereas the treatment with Novo-Helisen depot causes a diminution of bronchial specific and nonspecific reactivity and a negativisation of late allergic reaction.

[Effect of cetirizine, selective H1 antagonist of histamine on skin and bronchial reactivity and cellular histamine release in allergic diseases]. / Wplyw cetyryzyny, wybiórczego antagonisty receptora histaminowego H1 na reaktywnosc skóry i oskrzeli oraz komórkowe uwalnianie histaminy u chorych z odczynami alergicznymi.

The study aimed at evaluating an effect of cetirizine--selective antagonist of histamine H1 receptor--on skin and bronchial reaction to histamine, and histamine release from the cells by pollen antigen and anti-IgE. Skin reactivity was tested thrice in 33 patients treated with Zyrtec (Polfa) for the chronic urticaria or allergic rhinitis. Reaction of the bronchi to histamine was tested with a technique described by Ryan et al in 10 asthmatic patients. As effect of cetirizine on histamine release from neutrophils was evaluated in patients with pollinosis before and on the fourth day of therapy. It was shown that the treatment with Zyrtec markedly decreases skin reaction to histamine. Single dose of drug administered 4 hours before the tests markedly restricts reactivity of the bronchi. Daily dose of 10 mg administered to patients with pollinosis stabilizes membranes of neutrophils.

[Effect of ketotifen, nedocromil sodium and budesonide on non-specific bronchial hyperreactivity to histamine in patients with asthma]. / Wplyw ketotyfenu, nedokromilu oraz budezonidu na nadreaktywnosc oskrzli oceniana testem histaminowym u chorych na astme oskrzelowa.

The aim of the study was to evaluate the effect of ketotifen, nedocromil sodium and budesonide on non-specific bronchial hyperreactivity in asthmatic patients. The study was performed on a group of 40 patients treated with these drugs for a period of 4-12 weeks. Bronchial provocation with histamine was carried out in all patients before and after therapy. In subjects receiving ketotifen an additional provocation test was performed 3 days and 4 weeks after commencement of treatment. The results showed that drugs inhibiting the release of mediators from mast cells or diminishing the late phase of bronchial allergic reaction significantly reduce non-specific bronchial hyperreactivity.

[Clinical evaluation of broncho-vaxom efficiency]. / Kliniczna ocena skutecznosci preparatu Broncho-Vaxom.

Broncho-vaxom was administered to 40 patients with recurrent respiratory infections, allergic-infectious bronchial asthma and chronic bronchitis. Broncho-vaxom was administered in the dose of one capsule for the first month, and 1 capsule for 10 days in the third, fourth, and fifth month. A favourable clinical effect has been achieved in over 50% of the treated patients manifested by the decrease in the number and severity of respiratory infections and reductions in antibiotics use. These results confirm clinical efficiency of this vaccine.