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Biomedical subjects

B Schmekel

Publications and source records attributed to B Schmekel.

At least 37 records · Page 2Linked to original sources
PubMed1992

Lung function and immunopathological changes after inhaled corticosteroid therapy in asthma.

Six patients with asthma (American Thoracic Society (ATS) criteria), maintained on inhaled beta 2-agonists alone, were treated with inhaled corticosteroid (budesonide 400 micrograms b.d.) for a period of three months. Prior to steroid therapy, baseline spirometry, bronchodilator response and bronchial hyperresponsiveness were documented and endobronchial biopsies were obtained for immunopathological analysis. Frozen sections of the biopsies were investigated using immunoperoxidase methods, with a panel of monoclonal antibodies selected to reveal the presence and distribution of lymphocyte and macrophage subsets and HLA-DR expression. After three months the studies were repeated. Studies before steroid therapy revealed a T-cell-dominated inflammation in the bronchial wall of all subjects. Baseline airway obstruction, median (range) forced expiratory volume in one second (FEV1) 78.5 (61-109)% of predicted, with a significant bronchodilator response 20.8 (14-33)% and bronchial hyperresponsiveness to histamine geometric mean (SD) PC20FEV1 0.69 (2.5) mg was documented. Steroid therapy caused a significant reduction in bronchial hyperresponsiveness to histamine, with an increase in geometric mean PC20FEV1 to 2.22 (3.2) mg post steroid (p less than 0.03). Concurrent with a reduction in bronchodilator response and an increase in spirometric variables (improved forced midexpiratory flow (FEF25-75) p less than 0.03), there were marked reductions observed in the overall numbers of T-lymphocytes (CD 2, 5, 8), the numbers of CD45RO+ T-cells, and the numbers of macrophages (RFD1+) with the phenotype of antigen presenting cells. In all six subjects, reductions in the quantitative expression of HLA-DR molecules were also seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Recoveries of phosphatidylcholine and alveolar macrophages in lung lavage from healthy light smokers.

Twenty-one healthy volunteers, 11 light smokers and 10 non-smokers, were studied by broncho-alveolar lavage. The levels of the phosphatidylcholine (PC) in broncho-alveolar lavage were measured and used as an index of surfactant. The PC levels in broncho-alveolar lavage obtained from the smokers were significantly lower than in lavage fluid from the non-smokers. There was an inverse correlation between PC levels and cumulated tobacco smoke exposure, as estimated by the number of pack-years, and to current smoking habits as estimated by the number of cigarettes smoked per day. The number of alveolar macrophages was significantly higher in broncho-alveolar lavage obtained from smokers, and there was a significant inverse correlation between PC levels and numbers of alveolar macrophages in the lavage fluids. The potential role of alveolar macrophages in the elimination of surfactant lipids is discussed.

Adult↗
PubMed1991

T cell dominated inflammatory reactions in the bronchioles of asymptomatic asthmatics are also present in the nasal mucosa.

Endobronchial and nasal mucosa biopsies were obtained from 5 patients with clinically-stable, diagnosed asthma (ATS criteria). A comparison was made of the presence and distribution of immunocompetent lymphocytes and macrophages within each sample. The distribution of immunocompetent cells within the nasal biopsies of the asthmatic patients reflected a very similar inflammatory infiltrate to that seen in the bronchial biopsies. Significantly raised numbers of T lymphocytes, CD45RO + lymphocytes, RFD1 + macrophage-like cells and RFD7 + macrophages were seen in both the nasal mucosa and the bronchial biopsies. Increases in HLA-DR expression were also seen in the nasal mucosa biopsies from asthmatics although the increases over normal did not reach statistical significance. It is concluded that inflammation present in the nasal mucosa of asymptomatic asthmatics exhibits cellular characteristics also seen in endobronchial biopsies. This observation offers the possibility that mucosal biopsy may be an alternative and less invasive approach for studying the cells involved in the bronchial inflammatory reaction that possibly predisposes asthmatics to bronchial hyper-responsiveness.

Adolescent↗
PubMed1991

Difference in pulmonary absorption of inhaled terbutaline in healthy smokers and non-smokers.

Pathophysiological studies have shown that the alveolocapillary transfer of small solutes is much faster in healthy smokers than in non-smokers. The effects of smoking on the pulmonary absorption of inhaled terbutaline were examined in normal subjects. Nine healthy smokers and 13 healthy non-smokers inhaled nebulised terbutaline and dry terbutaline powder on two study days. Plasma concentrations of terbutaline were measured up to 240 minutes after the inhalation. The plasma concentration of terbutaline rose much faster in smokers than in non-smokers, the mean time to peak terbutaline concentration being 17 minutes in the smokers and 50 minutes in the non-smokers. The peak plasma concentration was nearly twice as high in the smokers as in the non-smokers, being 21 mmol/l and 23 mmol/l for the dry powder inhalation and nebuliser respectively in the smokers and 12 mmol/l and 14 mmol/l in the non-smokers. It is concluded that smoking increases the rate of terbutaline absorption and the peak plasma concentration achieved. The rapid pulmonary absorption of terbutaline in smokers may affect the onset of action of the drug and the duration of its therapeutic effects.

Administration, Inhalation↗
PubMed1991

Glucocorticoid receptor mRNA expression in pulmonary alveolar macrophages in sarcoidosis.

The presence of the glucocorticoid receptor was demonstrated by immunocytochemistry in pulmonary alveolar macrophages obtained by bronchoalveolar lavage. Also, GR mRNA content was determined by solution hybridization in PAM from 12 healthy volunteers and in 6 patients with sarcoidosis. No significant differences with regard to GR mRNA expression was detected between the two groups examined. For comparison, lung tissue from three patients undergoing thoracic surgery was examined and found to contain GR mRNA levels in the same range. As an indication of GR function, we also determined the mRNA levels of a glucocorticoid-regulated gene, metallothionein IIA, during basal conditions and after in vitro incubation of PAM with dexamethasone. Neither the control sample nor the dexamethasone-stimulated MTII mRNA values in PAMs differed significantly between the two groups. Solution hybridization is a rapid, sensitive and convenient assay which enables accurate and specific quantitation of GR mRNA in PAM. The GR mRNA content and basal as well as dexamethasone-induced MTII mRNA levels in PAM from patients with sarcoidosis is not significantly different from those in healthy volunteers.

Adult↗
PubMed1991

The distribution of myeloperoxidase, eosinophil cationic protein, albumin and urea in sequential bronchoalveolar lavage.

The distribution of myeloperoxidase (MPO) and eosinophil cationic protein (ECP), secreted from activated neutrophils and eosinophils, was estimated in bronchoalveolar lavage fluid in a sequential lavage study performed on 12 healthy subjects. Four 50 ml aliquots were sequentially injected into the right middle lobe and immediately aspirated. Recent studies, using radiological methods, have revealed proximal airway distribution of the first infused lavage aliquot, and more peripheral distribution of the following ones. We found significantly higher concentrations of MPO (p less than 0.001) and ECP (p less than 0.001) in the first aspirated aliquots as compared to the following three. These findings are compatible with the concept that these substances are, to a substantial part, distributed to the surface of the proximal airways. In contrast, the sequential recovery of albumin and urea showed a homogeneous recovery pattern. The findings were compatible with those of a small series of sixteen 10 ml lavage aliquots, sequentially infused and aspirated, also indicating a continuous diffusion of these small molecules through the lung membranes into the lavage fluid during the lavage process. We conclude that the difference in recovery pattern and distribution on the bronchial surface makes albumin and urea unsuitable as denominators in ratios to MPO and ECP, for the estimation of quantitative local concentration in epithelial lining fluid.

Adult↗
PubMed1991

Granulocytes and their secretory products, myeloperoxidase and eosinophil cationic protein, in bronchoalveolar lavage fluids from two lung lobes in normal subjects.

The interlobar variability of lavage neutrophils and eosinophils was studied in twelve healthy subjects. In addition, the interlobar variation of the neutrophil cell marker myeloperoxidase (MPO) and the eosinophil cell marker eosinophil cationic protein (ECP) was assessed. Bronchial washes (BW), as defined by the first aspirated lavage aliquot, and bronchoalveolar lavage (BAL) fluids were compared. One subsegment of the right middle lobe and one subsegment of the right lower lobe were lavaged in the same session. Interlobar consistency of neutrophil and eosinophil cell recoveries was observed but, in contrast, the levels of MPO or ECP did not correlate in lavage fluids aspirated from the two lobes. These results suggest that BAL cell content from a single lobe of the lung in healthy subjects does reflect the cell populations throughout the airways, while the levels of soluble proteins may differ between the lobes. Such a variation questions the correlation between cells and their secretory products or the correlation between levels of solutes in lavage fluid and in the underlying tissue. Further methodological studies appear warranted to elucidate whether cell and solute recoveries accurately reflect the underlying pathology.

Adult↗
PubMed1990

A critical view on lavage sampling techniques.

The constituents of the liquid aspirated in bronchoalveolar lavage are determined by the distribution of the fluid within the bronchial tree, the diffusion through membranes and the dilution by body fluids. Small volume lavages, sample cells, and soluble constituents from the surfaces of the proximal bronchial tree, and usually contain fewer cells than large volume bronchoalveolar lavages.

Bronchoalveolar Lavage Fluid↗
PubMed1990

Myeloperoxidase in human lung lavage. I. A marker of local neutrophil activity.

The origin of myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) was investigated in the first part of the study. Radioimmunoassay of the cellular and supernatant MPO content as well as the peroxidase-antiperoxidase (PAP) technique were employed to determine the cellular source of MPO. The concentrations of MPO were measured in serum and BAL in the second part of the study. The aim was to determine whether the capillary bed was also a source of MPO. Neutrophil numbers in BALs obtained from 20 healthy subjects correlated significantly to the concentrations of MPO in cell-free BAL supernatants (r = 0.643, P less than or equal to 0.01). The cellular content of MPO in mixed BAL cells was significantly correlated to the number of neutrophils in the mixture (r = 0.536, P less than 0.05), but not to the number of any other cells. Moreover, the PAP-technique identified MPO in lung tissue neutrophils in resection specimens obtained from three patients undergoing surgery. This technique also revealed strong MPO activity in all BAL neutrophils and a weak activity in merely 4% of the alveolar macrophages in cytospin preparations obtained from seven BALs. High BAL/serum ratio of MPO concentrations suggests that MPO is of local origin, rather than passively diffused from the circulating pool. We therefore conclude that strong evidence suggests that MPO in BAL originates from lung neutrophils and that BAL MPO content may be used to estimate the neutrophil presence or activation in epithelium lining fluid.

Adult↗
PubMed1990

Myeloperoxidase in human lung lavage. II. Internalization of myeloperoxidase by alveolar macrophages.

Bronchial wash and bronchoalveolar lavage were performed in 12 healthy subjects (five smokers), in order to elucidate whether or not material of neutrophil origin may be phagocytized by lung macrophages in vivo. Cells from different levels in the bronchial tree were obtained by sequential injection and subsequent aspiration of either four 50-ml or five 10-ml aliquots. Each aliquot was used for the determination of total and differential cell counts. The proportion of myeloperoxidase-positive alveolar macrophages was determined by specific immune histochemical staining. The percentage of myeloperoxidase-positive macrophages was highest (median 94.8%, range 37-98.5%) in the 10-ml aliquots and lowest in the last three 50-ml aliquots (median values 1-2.5%) (P less than 0.001). A significant correlation was obtained between the fraction of myeloperoxidase-positive macrophages and the percentage count of bronchoalveolar lavage neutrophils (r = 0.466, P less than 0.05). Furthermore, the cellular myeloperoxidase showed a significant inverse correlation (r = -0.46, P less than 0.05) to the viability of the bronchoalveolar lavage cells. Our findings are compatible with previous demonstrations in animals of neutrophil phagocytosis by lung macrophages and show that this phenomenon in particular occurs in the more proximal airways. The internalization of neutrophils or neutrophil components by airway macrophages may be an important scavenger mechanism for protection of the lung from the deleterious effects of activated neutrophils.

Adult↗
PubMed1990

Transfer of 99mTc DTPA and bronchoalveolar lavage findings in patients with asymptomatic extrinsic allergic alveolitis.

An investigation was performed to determine whether symptom free patients with previously diagnosed extrinsic allergic alveolitis had signs of inflammation in the lung. Pulmonary clearance of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (DTPA) was measured in seven patients with a history of extrinsic allergic alveolitis but with no symptoms at the time of the study and in 12 control subjects. Monoexponential clearance curves were obtained in all 12 control subjects. In contrast, lung clearance was abnormal in five of the seven patients: biexponential clearance curves were noted in four and an abnormally rapid monoexponential curve in one. Bronchoalveolar lavage was performed in all patients. Fluid from the second and third aliquots showed increased concentrations of albumin and urea in fluids from the patients, suggesting increased plasma leakage through the alveolocapillary membranes. More eosinophils and more eosinophil cationic protein were also found in the lavage fluid from the patients. The trend towards increased numbers of eosinophils in patients with abnormal lung clearance of DTPA suggests that this may be due to a continuing inflammatory reaction. Lung inflammation was also suggested by the fact that less leukotriene B4 was secreted by cultured alveolar macrophages obtained from patients than by control macrophages. It is concluded that symptom free patients with previous extrinsic allergic alveolitis have continuing alveolar disease as shown by lung clearance and lavage findings.

Adult↗
PubMed1985

Hyaluronate in bronchoalveolar lavage fluid: a new marker in sarcoidosis reflecting pulmonary disease.

Hyaluronate (hyaluronic acid) was not detectable in bronchoalveolar lavage fluid from smoking or nonsmoking healthy volunteers but was present in fluid from 23 patients with sarcoidosis; the mean concentration was 16 micrograms/1 returned fluid (range less than or equal to 5-430) or, expressed in relation to the amount of albumin recovered, 0.22 micrograms/mg albumin (range less than or equal to 0.05-3.6). The serum hyaluronate concentrations in the patients with sarcoidosis were normal. There was a significant inverse correlation between vital lung capacity and hyaluronate concentrations in bronchoalveolar lavage fluid (p less than 0.001), and patients with abnormal lung volumes had hyaluronate concentrations that were on average six times higher than those in patients with normal vital capacity. Duration of disease, pulmonary radiological findings, and markers for macrophage activation (angiotensin converting enzyme) and lymphocyte activation (beta 2 microglobulin) were not correlated with bronchoalveolar lavage fluid hyaluronate. It was concluded that in sarcoidosis release of hyaluronate into the airways is related to lung volume and therefore to the course of the disease. Increased synthesis of hyaluronate in lung parenchyma may reflect activation of fibroblasts, and measurements of hyaluronate may have clinical value for prognosis and treatment.

Adult↗
PubMed1985

C3b receptor-mediated phagocytosis in sarcoidosis with extra-thoracic manifestations.

Two groups of sarcoidosis patients were studied. One group of 24 patients had previously had erythema nodosum (EN+), and the other group of 54 patients had never had any such extrathoracic manifestation of the disease (EN-). The two groups were similar with respect to age, disease duration, chest radiographic appearance, and granuloma mass as estimated from the serum concentration of lysozyme. Neutrophil phagocytic function was studied by a kinetic method which allows distinction between Fc- and C3b-receptor-mediated uptake. Fc-receptor function was normal in both groups. The function of C3b receptors was normal in the EN+ groups but significantly reduced in the EN- group. This observation indicates that sarcoidosis associated with erythema nodosum may represent a separate disease entity with respect to the pathogenetic mechanism involved in granuloma formation.

Adult↗
PubMed1985

Neutrophil phagocytosis in sarcoidosis. Reduced C3b receptor-mediated phagocytosis in active and silent sarcoidosis.

The phagocytic and complement receptor function of polymorphonuclear neutrophils (PMN) from patients with sarcoidosis was studied using a kinetic assay which allows the distinction to be made between Fc receptor-mediated and C3b receptor-mediated particle uptake. The study included one group (A) of patients with active disease (n = 20), and one group (B) with silent or inactive disease who since 10 years had no symptoms or radiological signs of sarcoidosis (n = 11). Abnormal C3b receptor function was observed in both groups but the impairment was most pronounced in the A group. The presence of C3b receptor dysfunction in both groups with a quantitative difference between the groups, is compatible with C3b receptor dysfunction being a primary causal factor of sarcoidosis.

Adult↗
PubMed1984

Sarcoidosis: epidemiology and prognosis. A 15-year European study.

A 15-year study of patients with sarcoidosis is presented. In most patients, the disease was discovered at a general health screening examination. The mean total incidence among persons 15 yr of age or older was 19 per 100,000 per year (21.7 for women and 16.5 for men). There was a peak incidence in both sexes between the ages of 20 and 34, and in older women, there was a second but lower and broader peak. The frequency of symptoms was greater in older women than in other patients. The accumulated lifetime risk of sarcoidosis was 1.3% for women and almost 1% for men. Patients with Stage I sarcoidosis, i.e., with bilateral hilar adenopathy alone, had the best prognosis, with 50% of the patients showing a normal radiographic picture 15 months after the discovery of the disease. Among patients with Stage II sarcoidosis (both bilateral hilar adenopathy and pulmonary infiltration), it was 36 months before 50% returned to normal radiographically. Resolution of all radiographic evidence of the disease could still occur many years after the first pathologic findings were made on chest films.

Adolescent↗
PubMed1984

Serum-mediated stimulation and inhibition of neutrophil locomotion in sarcoidosis.

Chemotactic and chemokinetic activity was studied in sera from 57 patients with various stages of sarcoidosis. Reduced chemotactic activity was observed in 39% of the sera, mainly in sera from patients with parenchymal densities on chest radiographs. Increased chemokinetic activity was noted in more than one third of the fresh sarcoid sera. Asymptomatic patients showed higher chemokinetic activity in their sera than patients with symptoms. The presence of heat-stable chemokinetic inhibitors was suggested in one third of the cases. No relationship was found between these inhibitors and the inhibitors of neutrophil phagocytosis previously demonstrated in sarcoid sera. Although many of the findings show minor differences to those of normal sera, the liability in sarcoidosis to produce a variety of inhibitors directed against various functions of neutrophils would theoretically hamper the elimination of putative antigens. The presence of serum mediated stimulation and inhibition of neutrophil locomotion could be significant for the pathogenesis of the disease.

Aminopeptidases↗