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Biomedical subjects

J Małolepszy

Publications and source records attributed to J Małolepszy.

At least 19 recordsLinked to original sources

Relevance of the selected cytokine release (TNF-alpha, IL-6, IFN-gamma, and IFN-alpha) to the exacerbation of bronchial asthma from airway mycotic infections. Predominant role of TFN-alpha?

Airway fungal infections are often associated in asthmatics with the exacerbation of asthma symptoms. However, the pathomechanism of this phenomenon has not been fully understood. The aim of our study was to assess whether antimycotic treatment can influence the capacity of bronchoalveolar (BAL) leukocytes to release proinflammatory cytokines, which could contribute to increase in asthma severity. Ten patients with bronchial asthma complicated by airway fungal infections (Candida albicans and/or Aspergillus fumigatus) were included in the study. Seven asthmatics were treated with systemic and inhaled corticosteroids, whereas the remaining three with inhaled ones only. All subjects underwent several courses of therapy with antibiotics due to respiratory infections. BAL leukocytes obtained from the patients were cultured in the absence or presence of lipopolysaccharide E.coli (LPS) or Newcastle disease virus (NDV). The BAL procedure and measurement of the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (II-6), interferon-gamma (IFN-gamma), and interferon-alpha (IFN-alpha) by specific bioassays were performed twice: before antimycotic treatment and after 3 weeks of therapy with 8 mg of nebulized fluoconazole and 400 mg of oral ketoconazole per day. The elimination of fungi from respiratory tract resulted in an apparent clinical improvement. This coincided with diminished production of TNF-alpha in response to LPS and the production of IFN-alpha in response to NDV, which were initially high and subsided significantly after antimycotic therapy (p = 0.035, and 0.011, respectively). Such changes were not observed in the case of IFN-gamma and IL-6. This may suggest that TNF-alpha as well as IFN-alpha are secreted by fungi-prestimulated leukocytes from the lower respiratory tract and may be involved in the processes of exacerbation of asthma complicated by fungal infections. Further analyses of relationships between changes in cytokine levels and clinical parameters indicated that IFN-alpha seems to be of particular interest in fungal stimulation of asthma.

Adult↗

[Chylomicronemia syndrome in 45 years old man].

The case of chylomicronemia syndrome in 45 year old man, previously misdiagnosed as hypercholesterolemia is described. Secondary causes of hyperlipoproteinemia were excluded. No symptoms, characteristic of familial lipoprotein lipase deficiency were observed. We concluded that the diagnosis of hyperlipoproteinemia has to be based on determination of all plasma lipids concentrations (total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol). Otherwise a false diagnosis is quite possible. In rare cases additional laboratory tests are needed.

Chest Pain↗

[Influence of long-term low molecular weight heparin nebulization on selected clinical parameters and course of allergic inflammation in patients with bronchial asthma].

Bronchial asthma is a chronic condition with an inflammatory background--allergic inflammation. In recent years several observations have been published documenting activity of low molecular weight heparin (LMWH) in chronic inflammatory diseases of respiratory tract. This study was set up to evaluate the effect of nebulized LMWH on spirometric parameters and selected markers of allergic inflammation in bronchial asthma. Twenty patients diagnosed with mild or moderate asthma entered the study. At the beginning and at the end of the experiment every patient underwent bronchoscopy with BAL and in 15 of them bronchial biopsy was performed. Blood was drawn for ECP evaluation. LMWH was administered in nebulization in a dose 5000 U Xa/day for two weeks. BALf cellularity was evaluated as well as BALf IL-5 concentration. Further ELAM-1 and VCAM-1 expression in bronchial mucosa was examined in immunohistochemistry. We demonstrated that heparin treatment significantly enhanced FEV1 from 76.02 +/- 21.7% nominate value before to 92.4 +/- 21.8% after treatment (p < 0.005). Cellular profile of BALf changed, showing significant drop in percentages of eosinophils--from 7% to 6% (p < 0.05), macrophages--38 to 32% (p < 0.05) and neutrophils--32 to 28% (p < 0.05). Surprisingly we did not notice any change in ECP concentration in blood serum or IL-5 in BALf. Also adhesion molecules expression in bronchial mucosa remained unchanged. We conclude that chronic LMWH nebulization is a valuable treatment ameliorating asthmatic condition clearly due to anti-inflammatory properties of heparin. Both dose of LMWH used and the time of therapy have to be further investigated in order to develop treatment able to influence more of the elements of allergic inflammation.

Administration, Inhalation↗

[Evaluation of effectiveness and safety of three year immunotherapy with mixed grass pollen allergens].

BACKGROUND: Specific immunotherapy (SIT) is probably the only causative treatment in allergic diseases including pollinosis. It is capable of changing the natural history of the disease. GOAL: Present study has been designed to estimate the effectiveness and safety of multi-seasonal immunotherapy with grass-pollen-allergoid-containing vaccines. MATERIAL AND METHODS: Twenty seven patients with pollinosis entered the study. They were randomly assigned to two groups receiving two different but absolutely comparable vaccines (Allergovit, Pollinex). Cards of patient's self-evaluation (including nasal, eye and bronchial symptoms) as well as anti-allergic drug consumption were evaluated. RESULTS: Significant amelioration of symptoms was noticed already after first season of SIT 3.4 +/- 0.29 vs 7.54 +/- 0.35 points before SIT (control)(p < 0.05). The respective value after third SIT was 2.1 +/- 0.26 (p < 0.001). Also anti-allergic drug consumption felt from 2.12 +/- 0.12 points before SIT to 0.86 +/- 0.11 and 0.37 +/- 0.11 after first and third SIT, respectively (p < 0.001 and p < 0.00005). Few side reactions were observed, only one mild systemic reaction. CONCLUSIONS: Our study confirms that pre-seasonal SIT is a clinically effective and safe therapeutic method in patients with pollinosis. It's effect seems to be time-related.

Adolescent↗

Histamine receptor expression on peripheral blood lymphocytes is influenced by specific and nonspecific activation.

Histamine is a physiological mediator which exerts both effector and regulatory functions through its receptors on various cells. The aim of the study was to investigate changes in histamine receptor expression on peripheral blood lymphocytes affected by stimulation with both specific and nonspecific stimuli. Lymphocytes were obtained from both healthy and allergic subjects. Cells were incubated with various allergens (mixed grass pollen, Lolium perenne, Dermatophagoides pteronyssinus 1, bee venom, phospholipase A2) and nonspecific (fMLP, PMA/ionomycin, LPS) stimuli. The percentage of histamine-binding cells was determined with a fluorescence microscope after incubation with histamine-fluorescein. In control subjects histamine binding after stimulation with allergens was not significantly changed. In contrast, in allergic subjects stimulation with specific allergens resulted in significantly increased histamine binding. Nonspecific stimulation caused increased histamine binding to lymphocytes in both allergic subjects and healthy controls. We conclude that specific and nonspecific activation of lymphocytes is associated with increased expression of histamine receptors.

Adolescent↗

[Allergy to nickel, chromium and cobalt after osteosynthesis].

Metals are known as a common cause of contact allergies. The prevalence of sensitisation to the composite metals makes for a potential risk of osteosynthesis complications in patients suffering from long bones fractures. In the study the prevalence of delayed allergy to nickel sulphate, potassium dichromate and cobalt was estimated as well as the relation to the osteosynthesis complications. The atopy prevalence was estimated too. Persons under examination were divided into 3 groups. I--treated with osteosynthesis without complications (n = 20), II--treated with osteosynthesis with synostosis complications (n = 16) and III--negative controls (n = 34). We estimated 5% prevalence of delayed allergy to nickel in group I, 6.25% in group II and 5.8% in group III. In patients exposed to chromium we observed delayed allergy prevalence of 5.8% in group I and 3% in group III. No allergy to chromium in group II was revealed. No allergy to cobalt in all groups was revealed. The prevalence of atopy in group II was rare (6.35%) when in group I it was 45% and in controls 32%. The more frequent occurrence of type IV allergy to metals in atopic patients was not confirmed. There was no difference between the prevalence of delayed allergy to metals in groups I and II. Only one case of secondary allergy to chromium was observed.

Adolescent↗

Effect of recombinant IFN-gamma on igE-dependent leukotriene generation by peripheral blood leukocytes in patients with pollinosis and asthma.

Interferon gamma (IFN-gamma) is considered one of the causative and intensifying factors in inflammation. The reaction to allergens releases IFN-gamma, an immunomodulatory cytokine known to inhibit IgE synthesis and Th cell proliferation. The aim of the study was to evaluate the influence of IFN-gamma on leukotriene (LT) release in vitro, from human leukocytes of atopic patients with pollinosis and asthma. Thirty-eight patients were enrolled in the study: 15 with pollinosis and 23 asthmatics. In the presence of IL-3, leukocytes were stimulated with specific allergens. Other samples of leukocytes were preincubated with different concentrations of IFN-gamma for 15 min before allergen stimulation. The concentration of LT in supernatants was measured according to the CAST-ELISA procedure. We stated that IFN-gamma had significantly diminished LT release in a dose-dependent mode from the leukocytes of pollinotics. IFN-gamma did not change LT release in the asthmatic group, although, in leukocytes the small and medium basic production of LT, IFN-gamma caused a statistically significant fall in LT generation.

Adolescent↗

[Comparison of exercise and histamine provocation tests in patients with bronchial asthma].

Fifty-eight asthmatic patients (22 men and 36 women), aged 17 to 61 years, participated in this study. Thirty-two of them had atopic asthma. Exercise test and histamine inhalation challenge test were performed in all subjects. Patients exercised on a bicycle ergometer for 6-8 min. to increase the heart rate to 80% of predicted maximal heart rate. Twenty-three patients had a bronchospasm following exercise. The PC20 values in patients with exercise induced asthma (Me = 0.35 mg/ml) were significantly lower (p = 0.006) than in subjects without exercise induced asthma (Me = 1.89 mg/ml). There was low but statistically significant correlation between PC20 and delta FEV1 after exercise (R(s) = 0.32; p = 0.01). These results suggest that there are not only similarities but also differences in pathomechanisms of bronchial hyperreactivity to histamine and exercise-induced bronchoconstriction. The lack of statistically significant correlation between diurnal PEF variation and PC20 values suggest that the former parameter cannot be considered as an useful marker of nonspecific bronchial hyperreactivity.

Adolescent↗

[The effect of theophylline on neutrophil and lymphocyte chemotaxis stimulated with fMLP in health subjects and asthma patients].

Theophylline, for many years used as a bronchodilatator, is also known to have some anti-inflammatory properties. The aim of this study was to investigate the effect of theophylline on random locomotion and chemotaxis of neutrophils and lymphocytes from 12 patients with mild bronchial asthma and 12 healthy volunteers. fMLP in concentration 10(-8) M was used as a chemoattractant. The experiment was performed using the modified Boyden method. The cells were incubated with theophylline in therapeutic concentrations (from 5 to 20 micrograms/ml) at 37 degrees C for 30 minutes. Motility of neutrophils and lymphocytes was determined as the migration distance of the cell leading front inside the filter (micron). We found no statistically significant differences in both spontaneous and fMLP-stimulated cell motility between asthmatics and healthy subjects. fMLP-stimulated chemotaxis was significantly inhibited after neutrophil preincubation with theophylline in therapeutic concentrations (5-20 micrograms/ml) in both groups. Random locomotion of lymphocytes was slightly but significantly higher in healthy subjects comparing to asthmatics. Preincubation with theophylline at concentrations 10 to 20 micrograms/ml resulted in significant inhibition of fMLP-stimulated chemotaxis in both groups. Our data show the inhibitory action of theophylline on fMLP-induced chemotaxis of both neutrophils and lymphocytes indicating the anti-inflammatory activity of the drug.

Adult↗

[Bronchial hyperreactivity to histamine and levels of serum eosinophil cationic protein in patients with non-atopic asthma].

Pathogenesis of non-atopic bronchial asthma remains still an open question. Until now there have been very few studies concerning relationship between eosinophil activation and nonspecific bronchial hyperreactivity to histamine in this form of asthma. Sixteen subjects with mild nonatopic bronchial asthma entered the study. Evaluations of PC 20 for histamine and serum eosinophil cationic protein (ECP) concentration have been performed in all patients. In spite of fact that all patients were considered as mild asthmatic we have observed wide range of PC 20 and serum ECP concentration. Moreover we were able to find statistically significant inverse correlation between PC 20 for histamine and serum eosinophil cationic protein concentration: r = -0.498, p < 0.05. We conclude that eosinophil activation plays an important role in pathophysiology of nonspecific bronchial hyperreactivity in nonatopic bronchial asthma.

Adult↗

[Effects of anti-inflammatory drugs on adhesion and migration of lymphocytes].

The first crucial step of cell recruitment to the sites of inflammation is adhesion and motility, which are interdependent phenomena. The purpose of our study was investigate the influence used anti-inflammatory drugs (Aspirin, Cyclosporin A, Methotrexate) and endogenous substances of anti-inflammatory activity (Cortisol, TGF-beta) on these phenomena. Lymphocytes from healthy subjects were preincubated with various concentrations of these substances and adhesion to plastic bound CD11a/CD18, CD11c/CD18, CD44 and CD62L mAbs was determined. Simultaneously, cell motility was investigated after Boyden method. We found significant reduction of cell adhesion to all the ligands used. Furthermore we observed significant dose dependent increase in motility of these cells. These data indicate that simultaneous enhancement of motility and reduction of adhesion might be a common pathway for the mechanisms of action of anti-inflammatory agents.

Adult↗

[Validation of the Polish version of St. George's respiratory questionnaire in patients with bronchial asthma].

St George's Respiratory Questionnaire (SGRQ) has been widely used in the assessment of health related quality of life (HRQOL) in patients with asthma and chronic obstructive pulmonary disease. Introduction of the new language version of the HRQOL questionnaire needs to be preceded by a highly structured process of validation. We aimed to validate the Polish version of SGRQ in the group of 83 patients with asthma. Following the comprehension study, we thus evaluated reliability, validity, reproducibility, responsiveness, and measurement equivalence of the Polish version of SGRQ. Disease severity and health status were also concurrently assessed. The reliability was good, with Cronbach's alpha coefficient exceeding 0.75 for global and all subscale scores. There have been highly significant correlations between spirometric parameters, intensity of symptoms, health status self-assessment, and the degree of depression, and quality of life scores. Reproducibility, stability and responsiveness were confirmed in the follow-up study. Minimal clinically important difference was found to be 5.3 points. Polish version of SGRQ was found to be psychometrically equivalent to four other versions of SGRQ, which underscores its validity in the population of Polish asthmatics.

Adult↗

[The results of research on the prevalence of allergy to Hymenoptera venom in Southwestern Poland].

A questionnaire designed to estimate the prevalence of allergic reactions to Hymenoptera venom was posted to 1000 inhabitants of south west Poland. 881 persons responded to the questionnaire. 255 (28.9%) reported allergic reactions to stinging insects venom 141 persons (16%) report large local reactions (LL) and 114 (12.9%) systemic reactions (SYS) after stinging. At the second stage of the study 95 persons, out of the 255, were examined by a physician and tested with the intracutaneous skin test. Anamnesis carried out by the physician initially confirmed venom allergy in 87% of the LL group and 77.5% of the SYS group. Skin test results verified the above assessments confirming venom allergy in 38% persons initially reporting LL reactions and in 55% of those initially reporting SYS reaction.

Adolescent↗

[Toxic reaction induced by Hymenoptera stings].

Clinical symptoms of toxic reactions occurred in two patients following multiple stinging by bees and wasps respectively. The first cause is that of 76-year old woman attacked by a swarm of bees (about 200 stings), the other case presents a 69-year old man who was stung by several dozen of wasps. In the first case the toxic reaction was manifested by shock, acute renal failure, tissue damage of the skin, muscles and liver and haemolysis which resulted in the patients death. These symptoms occur as a results of the cytotoxic effects of bee venom components such as melittin, phospholipase and kinins. In the course of the disease, noteworthy are: the initial phase mimicking an anaphylactic shock, haemolysis and rhabdomyolysis which lead to acute renal failure with tubular necrosis. In the second case skin symptoms prevailed. Additionally, laboratory tests showed increased CPK as a results of myolysis caused by components of insect venom. The progress of toxic reactions following multiple stinging especially by bees, calls for hospital observation of stung patients with careful monitoring of renal function.

Acute Kidney Injury↗

[Specificity and sensitivity of some signs, symptoms and basic laboratory findings for differentiation between bronchial asthma and chronic obstructive pulmonary disease].

The aim of this study was to asses the importance of the most frequently observed signs and symptoms, as well as commonly used laboratory tests for differentiation between bronchial asthma and chronic obturative pulmonary disease (COPD). Sensitivity(Se) and specificity (Sp) indices were calculated for 140 analysed variables. Sixty one patients diagnosed as having COPD and 89 as suffering from asthma were analysed. For each patient the modified ATS-DLD-75-C questionnaire was filled out, and laboratory tests results were collected. Laboratory findings included: basic spirometry, diurnal PEF variation, bronchodilator tests with salbutamol, ipratropium bromide and corticosteroids, challenges with histamine and exercise, blood gas analysis, skin tests, chest X ray, ECG, blood cell count, blood and sputum eosinophilia. The results obtained have shown that there is no single parameter characterised by specificity and sensitivity that enable to differentiate between the diseases of interest with sufficient accuracy. Sputum expectoration for et least 3 months of the year (Se = 84%, Sp = 69%), smoking index (cigarettes number per day x years of smoking) > or = 200 (Se = 89%, Sp = 74%), have appeared to have the highest sensitivity and specificity for COPD. Most typical of asthma are: intermittent episodes of wheezing (Se = 89%, Sp = 69%), positive bronchodilator tests: with salbutamol (Se--73%, Sp--93%), with ipratropium bromide and with corticosteroids (Se--66%, Sp--94%) and diurnal variation of PEF > or = 20% predicted (Se--64%, Sp--92%). Challenge test with histamine is of limited value for differentiation bronchial asthma from COPD (Se--96%, Sp--40%), while blood eosinophilia, resting spirometry or blood gases are useless for this purpose.

Adult↗

Spontaneous motility and chemotaxis of neutrophils is influenced by glycocorticosteroid therapy.

The migration of neutrophils is an important part of the allergic inflammatory response. The aim of our study was to investigate the effect of glucocorticosteroids (GCS) on the stimulated and unstimulated migration of neutrophils. The study comprised 103 asthmatics including 44 subjects under GCS therapy (20 GCS resistant and 24 GCS sensitive) as well as 96 healthy control individuals. Unstimulated (random) motility as well as chemotactic response towards fMLP (10-8 mol/l) were determined after Boyden method. Neutrophil motility was determined by the distance of the leading front in filter. In both resistant and sensitive asthmatics under GCS therapy we observed significantly increased unstimulated motility as compared to normal controls (p < 0.001). However, this effect was not demonstrated in the GCS untreated group. Neutrophil chemotaxis towards fMLP was increased in GCS untreated group as compared to healthy controls (p < 0.05). In GCS sensitive subjects the chemotatic activity was decreased. In GCS resistant asthmatics it was moderately increased. We conclude that increased unstimulated neutrophil motility might be one of the immunosuppressive mechanisms of GCS by preventing the cell accumulation at the sites of inflammation.

Adult↗