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Biomedical subjects

D Bouros

Publications and source records attributed to D Bouros.

At least 19 recordsLinked to original sources

Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a deadly disease with no effective treatment. The purpose of this randomised prospective multicentric study was to characterise the clinical effects of interferon gamma (IFN-gamma) 1b administered subcutaneously thrice weekly versus colchicine for 2 yrs. This study had no pre-specified end-points. Fifty consecutive IPF patients were randomised. Patients with mild-to-moderate IPF were eligible for the study if they had histologically proven IPF, or, in the absence of surgical biopsy, fulfilled the European Respiratory Society/American Thoracic Society criteria. In the intent-to-treat population, five out of 32 (15.6%) IFN-gamma-1b patients and seven out of 18 (38.8%) colchicine patients died after a median follow-up period of 25 months Patients treated with IFN-gamma 1b showed a better outcome after 2 yrs of therapy, and fewer symptoms, as assessed using the St George's Respiratory Questionnaire, after 12 months of therapy. Also, the IFN-gamma-1b group exhibited a higher forced vital capacity (percentage of the predicted value) after 24 months of treatment. No significant differences were detected in resting arterial oxygen tension, total lung capacity (% pred), transfer factor of the lung for carbon monoxide (% pred) and high-resolution computed tomographic scoring between the two treatment groups. These data suggest that long-term treatment with interferon gamma 1b may improve survival and outcome in patients with mild-to-moderate idiopathic pulmonary fibrosis. Further studies are needed to verify these results.

Adult↗

Exhaled markers of oxidative stress in idiopathic pulmonary fibrosis.

BACKGROUND: Expired breath condensate (EBC) has never been used to explore the level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to measure the levels of H2O2 and 8-isoprostane, as biomarkers of oxidative stress, in the EBC of patients with IPF. MATERIALS AND METHODS: We investigated 16 patients with IPF and 15 healthy subjects as the control group. The levels of H2O2 and 8-isoprostane were measured in the EBC of all subjects and were compared between the IPF and control groups. In patients with IPF, H2O2 and 8-isoprostane were further correlated with pulmonary function tests (PFTs), the resting pO2 and the differential cell count from the bronchoalveolar lavage fluid (BALF). RESULTS: The mean (95%CI) concentration of H2O2 was increased in the patients with IPF compared with the normal subjects (0.36, 0.24-0.47 microM vs. 0.16, 0.10-0.23 microM, P=0.003). The mean (95%CI) concentration of 8-isoprostane was also increased in the patients with IPF compared with the controls (74, 38-110 pg mL-1 vs. 33, 28-39 pg mL-1, P=0.02). In the patients with IPF, the diffusing capacity of the lung for carbon monoxide was negatively correlated with the levels of H2O2 in EBC (P=0.03, r=-0.58). No other correlation was found between the oxidative stress markers in the EBC and PFT values, pO2 or BALF cell count. CONCLUSIONS: Our data suggest that H2O2 and 8-isoprostane are increased in the EBC of patients with IPF. H2O2 may be correlated with the severity of the disease in IPF.

Adult↗

Overexpression of bcl-2 protein in bronchoalveolar lavage lymphocytes and macrophages in sarcoidosis.

BACKGROUND AND OBJECTIVES: Apoptosis, also known as programmed cell death, probably correlates with the pathophysiologic mechanisms of alveolitis in sarcoidosis. Our purpose was to investigate any changes in the expression of the antiapoptotic protein Bcl-2, one of the most important inhibiting factors of apoptosis, in bronchoalveolar lavage fluid (BALF) cell populations in patients with sarcoidosis. SUBJECTS AND METHODS: Fiberoptic bronchoscopy with BAL was performed in 13 patients with active sarcoidosis (10 patients with stage I and 3 with stage II disease based on chest radiography). None of them was under treatment with corticosteroids. Cellular Bcl-2 expression was identified using an immunoperoxidase staining method. Ten normal subjects served as control group. RESULTS: BALF lymphocytes and macrophages in sarcoid patients exhibited a significant increase in the expression of Bcl-2 compared with the control group (p < 0.001). A Bcl-2 expression of 80.7 +/- 8.5% in the lymphocytes and 77.4 +/- 8.9% in the macrophages was observed in sarcoidosis versus 32.2 +/- 13.8% and 19.6% +/- 7.6% in normal subjects, respectively. The percentages of Bcl-2 expression in the lymphocytes were positively correlated with BALF CD4/CD8 ratio values (p = 0.02, r = 0.63). CONCLUSIONS: Our results suggest that the antiapoptotic protein Bcl-2 is overexpressed in alveolar lymphocytes and macrophages, which characterize the alveolitis in sarcoidosis and could provide insights into the pathogenesis of the disease and prove useful as a marker of disease activity or response to therapy.

Adult↗

Current and future therapeutic approaches in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal form of idiopathic diffuse lung disorders for which no current treatment is effective. The aim of the present study was to systematically review the current status and novel therapies of IPF, with emphasis on controlled trials. The studies selected included randomised controlled trials using drugs alone and/or in combination for the treatment of adults with IPF and meta-analyses, published in English. Abstracts of identified articles were retrieved and articles possibly fulfilling inclusion criteria were retrieved in full. Two reviewers independently assessed trial quality if there were any included studies. Data quality was based on place of publication and relevance to clinical care. There is a lack of good-quality studies regarding the effectiveness of the most used drugs, including corticosteroids and noncorticosteroid immunosuppressive agents. Oral corticosteroids are the usual treatment. Other therapies either alone or in combination with corticosteroids are widely used, including azathioprine, cyclophosphamide and colchicine. Interestingly, clinical trials with novel drugs, mainly antifibrotic, anticytokine and immunoregulatory, are currently being investigated in various trial phases. In conclusion, at present, there are no evidence-based therapies for idiopathic pulmonary fibrosis. Further controlled studies are warranted to improve the evidence base for clinical practice.

Clinical Trials as Topic↗

Nosocomial lower respiratory tract infections: prevalence and risk factors in 14 Greek hospitals.

Nosocomial lower respiratory tract infections (NLRTIs) are associated with significant morbidity and mortality. The aim of this study was to investigate the epidemiological features of NLRTIs in Greece, where knowledge about these infections is limited. Two point-prevalence studies of hospital-acquired infections were carried out in 14 Greek hospitals located throughout the country, one in 1999 and one in 2000. NLRTIs were diagnosed in accordance with the Centers for Disease Control and Prevention (CDC) definitions. Among the 7,120 hospitalized patients registered during the two studies, 610 (8.6%) cases of hospital-acquired infections were identified, of which 200 (32.8%) were NLRTIs. Sixty-nine (34.5%) patients had pneumonia, and the remaining 131 (65.5%) patients had bronchitis. The greatest prevalence of NLRTI was found in the adult ICUs (30.4%). Male gender, age >65 years, mechanical ventilation, tracheostomy, an intravenous central line, and an indwelling urethral catheter were the main risk factors. There was no significant difference in the incidence of NLRTI among hospital-acquired infections between the 1999 study and the 2000 study. The causative microorganism was identified in 78 of 200 (39%) cases, and 103 strains were isolated. The majority of strains (67%) were gram-negative bacteria. The most frequently isolated microorganisms were Pseudomonas aeruginosa (22.3%), Acinetobacter spp. (19.4%), Klebsiella pneumoniae (12.6%), and Staphylococcus aureus (10.7%). There was no difference between the two prevalence studies in the frequency of isolation of the microorganisms. NLRTI was the leading cause of morbidity and mortality among hospitalized patients with hospital-acquired infections in Greek hospitals. Gram-negative microorganisms were the most frequently isolated pathogens.

Aged↗

Fine-needle aspiration cytology of a para-aortical solitary plasma-cell tumor.

Extramedullary plasma-cell tumor (EMP) is a very rare disease and mainly arises in the head and neck area. An EMP arising in the paraaortical space was diagnosed by fine needle aspiration cytology and immunocytochemistry, in a 48-year-old male. Smears were cellular and showed dissociated monomorphic plasma cells. Immunocytochemistry demonstrated monoclonal expression of kappa-light immunoglobulin chain and CD38 positivity. Cytomorphology and immunocytochemical profile allowed a definitive diagnosis of plasmacytoma.

Aorta↗

Association between increased levels of IL-2 and IL-15 and outcome in patients with early acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome remains a serious, often fatal, condition, despite progress in modern critical care treatment. Cytokines play an important role in the pathogenesis of the syndrome, although their role in the evolution and outcome has not been clearly elucidated. We explored whether the measurement of serum and bronchoalveolar lavage IL-2 and IL-15 at the time of hospital admission can predict the outcome of this syndrome. METHODS: Serum and bronchoalveolar lavage levels of IL-2 and IL-15 were measured in eight patients with ARDS (group A) and 26 patients on high risk for ARDS development who never developed ARDS (group B) from samples obtained at the time of admission. RESULTS: Serum IL-2 (P > 0.05) and IL-15 (P < 0.05) levels were higher in group A than in group B. Serum levels of both cytokines were higher in patients who did not survive in both of the groups A and B compared to those who survived (P < 0.05, and P < 0.0001, respectively). The only significant change in BALF was the higher level of IL-15 in surviving group A patients (P < 0.05) when compared with the non survivors of the same group. For a serum cut-off level of 173 pg mL(-1) for IL-2 and 250 pg mL(-1) for IL-15, they exhibited a very high positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for survival (100% in all). A positive correlation was found between serum levels of both cytokines and APACHE II score (IL-2, r = 0.61, and IL-15, r = 0.62, respectively, and P < 0.0001 for both). CONCLUSION: Determination of serum IL-2 and IL-15 levels may be a valuable and simple aid to improve identification of patients with ARDS or at risk for ARDS who are at high risk of subsequent mortality.

APACHE↗

Serum proinflammatory cytokines and its relationship to clinical parameters in lung cancer patients with reactive thrombocytosis.

Proinflammatory cytokines Interleukin-1 beta (IL-1 beta) and Interleukin-6 (IL-6) play a significant role in the pathogenetic processes related to various malignant and inflammatory conditions. Leukocytosis, thrombocytosis and increased acute phase protein levels are part of a systemic inflammatory response. In this study, we measured the concentrations of IL-1 beta, IL-6 and ferritin as well as hemoglobin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in 23 patients (male 15, female 8, median age 68 years) with lung cancer and reactive thrombocytosis (LCRT), in 27 (male 18, female 9, median age 64 years) with benign inflammatory lung disorder (BILD) and 18 (male 10, female 8, median age 62 years) lung cancer patients with a normal platelet count (LCNP). IL-1 beta levels were significantly higher in the three patient groups in comparison with control subjects (P < 0.001) but without significant difference among the three patient groups. IL-6 was higher in all three patients groups but only in the BILD group it was significantly higher than the control group (P < 0.05). However, no significant difference in IL-6 serum levels was found between the two lung cancer groups. CRP and LDH were significantly higher in the LCRT group in comparison with the other two patient groups (P < 0.01 and 0.001, respectively), while ferritin was higher in both lung cancer groups in comparison with the BILD group (P < 0.001). Our data suggest that in lung cancer patients, reactive thrombocytosis is part of the systemic inflammatory reaction for which IL-1 beta and IL-6 may be intermediate but not independent mediators.

Adult↗

The role of video-assisted thoracoscopic surgery in the treatment of parapneumonic empyema after the failure of fibrinolytics.

BACKGROUND: Approximately 10% of patients treated with intrapleural instillation of fibrinolytics fail to respond and therefore need more invasive techniques, such as video-assisted thoracoscopic surgery (VATS). METHODS: During the period 1994-99, we treated 20 consecutive patients with complicated parapneumonic effusion (CPE) and pleural empyema (PE) that did not resolve with urokinase instillation given through the chest tube in a dose of 100,000 IU diluted in 100 ml of normal saline/daily for 3-5 days. The patients' ages ranged from 21 to 68 years (median, 46); 14 were male and six female. All patients had pleural fluid pH <7.1, LACTATE DEHYDRAGENASE (LDH) >1000, glucose <40 mg/dl and were submitted to VATS. RESULTS: Complete drainage was observed in 17 patients (85%), in the other three (15%), the procedure had to be converted to open thoracotomy due to a thickened visceral pleural peel. The mean operative time was 80.3 min (range, 55-140), and the mean duration of postoperative hospital stay was 7.5 days (range, 4-19). CONCLUSION: We found that VATS is a safe, effective, and well-tolerated surgical procedure in CPE and PE patients who have failed to resolve with initial treatment with fibrinolytics.

Empyema, Pleural↗

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↗

Availability of antidotes in hospital pharmacies in Greece.

We determined the availability of poisoning antidotes in the pharmacies of state hospitals in Greece and in Health Centers of the island of Crete. A questionnaire survey was sent to all pharmacy directors of hospitals with emergency departments, asking them to report anonymously the amount currently in stock of each of 12 common antidotes. Questionnaires were sent to 100 pharmacy directors and 68 (68%) of them replied. Only 2 (3%) of the 68 hospitals stocked all 12 antidotes. The percentage of sufficient stocking for individual antidotes ranged from 6% (for digoxin immune fab) to 91% (for methylene blue). Recent circulation of government guidelines for antidote stocking and hospital type had no significant effect on antidote stocking. In a multiple regression analysis, hospital type (prefectural, regional, university hospital) and smaller hospital size were not predictors of the number of antidotes sufficiently stocked. Storing of key poisoning antidotes is inadequate in regional as well as in prefectural hospitals in Greece. Antidotes, including those which should be used without delay to be effective, are often not available, even for the commoner poisons in Greece such as pesticides.

Antidotes↗

Pulmonary sarcoidosis. Correlation of expiratory high-resolution CT findings with inspiratory patterns and pulmonary function tests.

PURPOSE: To assess the presence and extent of air trapping (AT) on chest high-resolution CT (HRCT) in sarcoidosis and to correlate such findings with patterns, lesion extent on inspiratory CT and pulmonary function tests (PFT). MATERIAL AND METHODS: Thirty patients with sarcoidosis underwent inspiratory and expiratory HRCT and PFT. HRCT images were evaluated for presence, distribution and AT extent as well as the predominant HRCT pattern and the extent of lesions at inspiration. Attenuation difference in the AT regions at expiration and at inspiration were calculated. The presence and extent of AT were correlated with PFT, extent of involvement and predominant inspiratory patterns. RESULTS: AT was present in 25/30 patients with no lung zone predilection. AT was the only CT indication of pulmonary sarcoidosis in 3/30 patients who also had normal PFT. Attenuation difference between inspiration and expiration ranged from -40 HU to 106 HU. In 2 patients, a paradoxical decrease of lung attenuation was observed at expiration. A significant correlation was found between AT extent at expiration, with residual volume-total lung capacity ratio and residual volume. CONCLUSION: AT is an additional HRCT finding in sarcoidosis. AT may involve any lung zone, including costophrenic angles and may be the only CT feature of pulmonary sarcoidosis. Strong correlation is only found with PFT values that are specific for incomplete lung emptying at expiration.

Adult↗

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↗

Genetic predisposition and pathogenetic mechanisms of interstitial lung diseases of unknown origin.

Understanding of the cellular and cytokine interactions associated with inflammation and fibrosis in interstitial lung diseases (ILDs) has increased substantially during the past few years. Presently, many agents are known to have the ability to induce ILDs, although only a small percentage of exposed individuals will develop the disease. In addition, the majority of ILDs are of unknown origin and many are labelled "idiopathic". Therefore, host susceptibility, genetic factors and, possibly, environmental cofactors may be important for the clinical expression of ILDs. The present review reports evidence of the genetic predisposition to develop ILDs of unknown origin, more specifically sarcoidosis, idiopathic pulmonary fibrosis (IPF), lymphangioleio-myomatosis and ILDs, in systemic sclerosis. For instance, for sarcoidosis and IPF several histocompatibility antigens have been associated with the development and/or the clinical presentation of the disease. Furthermore, there are also several types of ILD that are associated with inherited disorders, of which the tuberous sclerosis complex is only one example. This clearly indicates that pulmonary fibrosis can be influenced by genetic factors. Familial occurrence of sarcoidosis and IPF is also well known, although the exact modes of inheritance are debatable. Several studies have shown that extrinsic factors, such as single or multiple fibrosing agents, probably contribute to the development of clinical ILDs of unknown origin. It is probable that some of these studies deal with patients who do not have classical IPF, as recently defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus. Therefore, the true role of these extrinsic factors in the development of IPF, or even sarcoidosis, remains speculative. With the help of animal studies and, more specifically, by using knock-out mice, it may be possible in the near future to unravel at least some of the genes that are responsible for the increased susceptibility of the development of interstitial lung diseases.

Animals↗

Acute interstitial pneumonia.

The term "acute interstitial pneumonia" (AIP) describes an idiopathic clinicopathological condition, characterized clinically by an interstitial lung disease causing rapid onset of respiratory failure, which is distinguishable from the other more chronic forms of interstitial pneumonia. It is synonymous with Hamman-Rich syndrome, occurring in patients without pre-existing lung disease. The histopathological findings are those of diffuse alveolar damage. AIP radiologically and physiologically resembles acute respiratory distress syndrome (ARDS) and is considered to represent the small subset of patients with idiopathic ARDS. It is frequently confused with other clinical entities characterized by rapidly progressive interstitial pneumonia, especially secondary acute interstitial pneumonia, acute exacerbations and accelerated forms of cryptogenic fibrosing alveolitis . Furthermore, many authors use the above terms, both erroneously and interchangeably. It has a grave prognosis with >70% mortality in 3 months, despite mechanical ventilation. This review aims to clarify the relative clinical and pathological issues and terminology.

Diagnosis, Differential↗