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Biomedical subjects

N M Siafakas

Publications and source records attributed to N M Siafakas.

At least 19 recordsLinked to original sources
PubMed2003

Induced sputum in the investigation of airway inflammation of COPD.

During the last decade, the method of sputum induction (SI) has offered the opportunity to study inflammation in patients with chronic obstructive pulmonary disease (COPD). This paper reviews methodological aspects of SI and summarizes its uses in the research of inflammation in COPD, including sputum cellularity and soluble markers. SI is a relatively safe, reliable, and reproducible technique, used to investigate different aspects of airway inflammation. Although various methods of induction and processing have been proved safe and highly reproducible, a generally accepted method is needed. Sputum analysis has given evidence for increased numbers of macrophages and neutrophils in COPD patients compared to normal subjects. In some studies, increased numbers of eosinophils have been also reported. Changes in various mediators have been found in sputum supernatant of COPD patients (IL-8, LTB-4 and TNF-a). The clinical usefulness of the method in the follow-up of the disease has not been explored extensively. A number of observations in patients with different clinical characteristics could be proven useful in identifying patterns of inflammation associated with different prognosis. Finally, SI could also guide treatment; such as, sputum eosinophilia in COPD could predict response to inhaled corticosteroids.

Biopsy↗
PubMed2002

Few smokers develop COPD. Why?

COPD is a common disease and its major risk factor, cigarette smoking, has been identified. However, only a minority of smokers develop clinically relevant disease. Although, the current understanding of the pathogenesis includes an "abnormal inflammation" as a response to various noxious agents, its various pathways are not clear. Oxidative stress, inflammation, tissue damage and tissue repair (remodeling) are parts of the complex procedure leading to COPD. This is a review of the available literature concerning the "susceptible" smoker. An epidemiological model is discussed, putting emphasis on the timing of the exposure to cigarette smoke. There are evidences that respiratory adenoviral infection in early life could be also an important factor. Differences in nutrition could also play a role in protecting against the oxidative stress. Airway hyperresponsiveness failed to clarify the whole picture and is still open for debate. Genetic differences are the most likely explanations to describe the "susceptible" smoker. However, the only well-established genetic risk factor is the alpha-l-antitrypsin. Other candidate genes were reviewed, alpha-l-antichymotrypsin, blood group antigens, vitamin-D binding protein, a2-macroglobulin, immunoglobulin deficiency, extracellular superoxide dismutase, secretory leukocyte proteinase inhibitor, cathepsin G, tumor necrosis factor-a gene and others. Microsatellite DNA instability in COPD could be a useful tool to identify the locus of genetic alterations leading to COPD. Thus, in addition to exposure to exogenous factors, host factors, most likely several genes, are involved and affect various pathways of the pathogenesis of COPD.

Bronchitis, Chronic↗
PubMed2001

Assessing the knowledge of bronchial asthma among primary health care physicians in Crete: a pre- and post-test following an educational course.

AIM: To assess the level of knowledge for bronchial asthma of the primary healthcare physicians serving a rural population on the island of Crete, both before and immediately after a one-day educational course. METHODS: Twenty-one primary health care physicians, randomly selected from a list of 14 Health Care Centres on the island of Crete were invited to participate in the study and attended an educational course. Nine of the 21 physicians were fully qualified general practitioners, while the remainder were non-specialized (NSs) physicians who had recently graduated from the University of Crete, Medical School. A questionnaire of 20 items based on current bronchial asthma clinical guidelines was used. Three scores, the mean total, knowledge subscore and attitudes subscore, were calculated for each group of physicians, both before and after the course. RESULTS: At baseline mean total score and knowledge and attitudes subscores were higher for non-specialized physicians than for the general practitioners, but the differences were not statistically significant (p > 0.05). The knowledge subscore was improved in both groups, however the difference was statistically significant only for the non-specialized physicians (t = 2.628, d.f. = 11, p < 0.05). The mean total score after the course was significantly higher for the non-specialized physicians in comparison to that of the general practitioners (t=-2.688, d.f. = 19, p < 0.05). CONCLUSIONS: This study adds to the information about the success of continuing medical education, and also demonstrates that the recent graduates in the studied population, could be educated with more positive results than the fully qualified practitioners

Asthma↗
PubMed2001

Diaphragmatic angiogenic growth factor mRNA responses to increased ventilation caused by hypoxia and hypercapnia.

This study investigates the effect of increased ventilation on the expression of messenger ribonucleic acid (mRNA) levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-beta1) in the diaphragm of intact, awake, spontaneously breathing rats, compared with responses in paralysed, mechanically-ventilated animals at similar blood gas and ventilatory levels. Four groups of intact, rats were studied in a body box, each group breathing one of four gases: room air, 12% oxygen (O2), 5% carbon dioxide (CO2), or 12% O2+5% CO2 for 1 h. Another 4 groups of paralysed, mechanically-ventilated animals were matched for arterial blood gas and ventilatory level. The results showed that VEGF mRNA abundance was increased three-fold and that of bFGF 1.5-fold when 12% O2+5% CO2 were breathed, but TGF-beta1 did not change. A significant linear relationship of VEGF and bFGF mRNA to minute ventilation was observed in awake animals (r=0.98, p<0.02 and r=0.87, p<0.03, respectively). The paralysed, mechanically-ventilated animals showed no mRNA increases for any probe. Systemic hypoxia had no additional effect on VEGF or bFGF levels in the diaphragm. It was concluded that messenger ribonucleic acid for vascular endothelial growth factor and basic fibroblast growth factor in the diaphragm rises significantly as a result of active ventilation and not due to blood gas/pH changes or to passive muscle shortening per se.

Animals↗
PubMed2001

Short-term effects of wood smoke exposure on the respiratory system among charcoal production workers.

STUDY OBJECTIVES: We aimed to investigate the short-term respiratory effects of heavy, occupational wood smoke exposure among traditional charcoal production workers. PATIENTS AND SETTING: A total of 22 charcoal workers (mean age, 41 years; 9 current smokers, 5 ex-smokers, and 8 nonsmokers) were studied and compared with a control group of 35 farmers residing in Perama, Rethymnon, Crete. RESULTS: The charcoal workers were exposed to wood smoke for an average of 14 h/d during a mean of 23.7 days required for the burning of kilns. The workers under study were found to have significantly more cough (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.2 to 19.7), sputum production (OR, 6; 95% CI, 1.4 to 26.5), wheezing (OR, 7.7; 95% CI, 1.4 to 41.5), dyspnea (OR, 28.7; 95% CI, 5.4 to 153), and hemoptysis (OR, 2.7; 95% CI, 0.7 to 55) than the control group. The prevalence of respiratory symptoms such as cough, sputum production, wheezing, and dyspnea in the charcoal workers was significantly elevated during the exposure period (OR, 5.4; 95% CI, 1.1 to 17.7; OR, 5.7; 95% CI, 1 to 31; OR, 9.8; 95% CI, 1 to 88; and OR, 36.7; 95% CI, 1 to 327, respectively). The mean +/- SD percent of predicted values of FVC, FEV(1), FEV(1)/FVC ratio, and forced expiratory flow at 25 to 75% of FVC during the exposure period were significantly lower than those before exposure: 106 +/- 10.8 vs 101 +/- 11.9, p < 0.01; 104 +/- 16 vs 97 +/- 15, p < 0.001; 81 +/- 9 vs 78 +/- 8, p < 0.001; and 95 +/- 27 vs 80 +/- 25, p < 0.01, respectively. The mean +/- SD value of peak expiratory flow at midday and in the evening during the exposure were significantly lower than before: 524 +/- 131 L/min vs 548 +/- 108 L/min, p = 0.03; and 521 +/- 135 L/min vs 547 +/- 131 L/min, p = 0.02, respectively. CONCLUSIONS: Our results suggest that wood smoke exposure in charcoal workers is associated with increased respiratory symptoms and decreased pulmonary function. Longitudinal studies are needed to determine potential long-term adverse respiratory effects.

Air Pollutants, Occupational↗
PubMed2001

Extended genetic alterations in a patient with pulmonary sarcoidosis, a benign disease.

BACKGROUND: Genetic alterations at the microsatellite level have been detected in various human malignant tissues, but have also been found in chronically inflamed tissues. Sarcoidosis is a benign disease of unknown etiology characterized by chronic inflammation, which may be associated with an increased incidence of developing malignancy. METHODS: We examined the microsatellite alterations in a sputum cytological specimen of a patient with sarcoidosis. The DNA electrophoretic pattern of sputum was compared with that of the peripheral blood. Thirty-two microsatellite markers located at chromosomes 2p, 3p, 8p, 9p, 9q, 17p, 17q were used to reveal genetic alterations. RESULTS: Loss of heterozygosity (LOH) was detected in eleven markers in loci 2p, 9p, 9q and 17q. LOH was observed in all four markers spanning the chromosomal arm 17q11.2-q21, suggesting a potential chromosomal deletion. CONCLUSION: The observation of LOH in all four markers spanning the chromosomal arm 17q11.2-q21 may suggest a potential for malignancy development in this patient, or may be linked to the aetiopathogenesis of sarcoidosis. Further microsatellite fine mapping and clinical follow up of this patient are needed to clarify this.

Adult↗
PubMed2001

Induced sputum in asthma.

This is a short review of the use of induced sputum in bronchial asthma. The clinical applications, the procedure of this method as well as the safety validity and reproducibility of the results are discussed in detail. It is shown that sputum induction is a practical and safe procedure and an important research tool of local inflammation of bronchial asthma.

Asthma↗
PubMed2000

Effect of digoxin on global respiratory muscle strength after cholecystectomy: a double blind study.

BACKGROUND: Upper abdominal surgery has been shown to impair the function of the respiratory muscles. In addition, controversial results have been reported concerning the effect of digoxin on the diaphragm. The aim of this study was to investigate further the mechanism(s) of respiratory muscle dysfunction after cholecystectomy and the effect of digoxin on the impaired respiratory muscle function. METHODS: Twenty three patients (four men) were studied before and 48 hours after surgery. Eleven received digoxin and 12 placebo. Respiratory muscle strength was assessed 48 hours after surgery by measuring mouth pressure during maximum static inspiratory (PImax) and expiratory (PEmax) efforts before and after 90 minutes of intravenous administration of 0.25 mg digoxin in a double blind, placebo controlled fashion. In addition, spirometric and pain measurements were performed. RESULTS: Postoperatively (+48 h) PImax and PEmax decreased significantly (p<0.01) from their preoperative values in both groups by a similar degree. After administration of digoxin or placebo only the digoxin group showed a significant increase in both PImax (p<0.02) and PEmax (p<0.05) with a mean increase of 15% for PImax and 12.3% for PEmax. The mean difference in PImax (DeltaPImax) and PEmax (DeltaPEmax) between the digoxin and placebo groups was 1.01 (95% CI 0.28 to 2.2) and 1.05 (95% CI 0.04 to 2.4), respectively. Estimates of postoperative pain did not differ between the two groups. Spirometric indices showed a similar restrictive defect postoperatively in both groups but did not change after digoxin or placebo. CONCLUSION: Digoxin improves the impaired global strength of the inspiratory and expiratory muscles after cholecystectomy and this may be clinically relevant. Muscle contractility could play a part in this impairment.

Adult↗
PubMed2000

Miliary sarcoidosis following miliary tuberculosis.

A patient who presented with a miliary radiographic pattern due to tuberculosis and later with a similar miliary pattern due to sarcoidosis is described. The patient, a 47-year-old man, was admitted to the hospital due to coughing, weakness, weight loss and an abnormal chest radiograph with a miliary pattern. A gastric fluid culture was positive for Mycobacterium tuberculosis and he was treated appropriately. He showed complete clinical and radiological remission. One year later he presented with a dry cough and a similar miliary pattern on the chest roentgenogram. Lung biopsy taken by thoracoscopy revealed sarcoidosis. The patient had a complete remission with corticosteroids. To our knowledge, this is the first report describing a miliary pattern as presenting radiological sign in a patient with tuberculosis who subsequently developed a new miliary pattern due to sarcoidosis.

Adrenal Cortex Hormones↗
PubMed2000

Frequent genetic alterations at the microsatellite level in cytologic sputum samples of patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology associated with DNA damage and malignancy. Bronchogenic carcinoma is the cause of death in 10% to 13% of IPF patients. Microsatellite instability (MSI) and loss of heterozygosity (LOH) are frequently detected in cancers. If these genetic alterations could be observed in IPF, they might explain the higher relative risk of lung cancer in this disease. We investigated the incidence of MSI and LOH in sputum cytologic specimens from 26 IPF patients and 26 healthy, matched subjects, using 10 highly polymorphic microsatellite markers. The electrophoretic pattern of each specimen was compared with that of corresponding peripheral blood. Thirteen (50%) patients showed genetic alterations, consisting either of MSI or LOH. Five (19%) patients exhibited MSI and 10 (39%) exhibited LOH in at least one microsatellite marker. Three (12%) patients showed LOH in more than one marker. None of the healthy subjects exhibited genetic alterations in the studied markers. No correlation was found between the detected genetic alterations and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings suggest that the genetic alterations that we studied are frequent in IPF, are apparently unrelated to the severity of the disease, and may be related to tumorigenesis.

Aged↗
PubMed1999

Pneumoconiosis among Cretan dental technicians.

Pneumoconiosis among dental technicians has recently emerged as an area of research in interstitial lung disease. This study was carried out to estimate the prevalence of pneumoconiosis in Greek dental technicians on the island of Crete. Fifty-one of the 58 dental technicians of the Heraklion Dental Technicians' Association completed an exposure history questionnaire and underwent a clinical examination, including chest radiographs, and spirometric assessment of lung volume and diffusing capacity. Values were compared with 51 control subjects. Five dental technicians showed radiological evidence of pneumoconiosis. Mean lung function values of the dental technicians, even in those with pneumoconiosis, were not significantly different from controls. No significant changes in lung function parameters were associated with smoking, exposure to metals and other contaminants. Dental technicians, however, reported more respiratory symptoms than controls (p = 0.008). Symptoms were associated to the absence of a ventilation system. We concluded that occupational exposure in dental technicians in Crete did not affect lung function. The prevalence of pneumoconiosis in this study was 9. 8%.

Adult↗
PubMed1999

Microsatellite DNA instability and loss of heterozygosity in pulmonary sarcoidosis.

In the present study we investigated the incidence of microsatellite instability (MI) and loss of heterozygosity (LOH) in sarcoidosis, a multisystem disease of unknown origin. We examined sputum cytological specimens from 30 patients with sarcoidosis and 30 healthy, matched subjects, using 10 highly polymorphic microsatellite markers located at several chromosomal arms. The electrophoretic pattern of each specimen was compared with the corresponding pattern of peripheral blood and any difference in the mobility of the microsatellite alleles was interpreted as MI-positive. LOH was scored as decrease in intensity of one allele relative to the other as determined from comparison of sputum and normal (blood) DNA. We found that 14 (47%) sarcoidosis patients showed genetic alterations, either MI or LOH. Six (20%) patients exhibited MI and nine (30%) exhibited LOH in at least one microsatellite marker. One of the patients exhibited MI in two microsatellite markers and three (10%) showed LOH in more than one marker. One patient showed complete deletion of the chromosomal arm 17q11.2-q21. None of the healthy subjects exhibited any genetic alteration in the studied markers. No correlation was found between the genetic alterations detected and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings suggest that MI is a detectable phenomenon in sarcoidosis and seems not to be related with the severity of the disease. The detection of LOH indicates the presence of putative tumor suppressor genes at loci examined, which may play an important role in the etiopathogenesis of sarcoidosis.

Adult↗