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Biomedical subjects

Y Pacheco

Publications and source records attributed to Y Pacheco.

At least 19 recordsLinked to original sources
PubMed2006

Management of asthma in patients supervised by primary care physicians or by specialists.

French asthma patients may be supervised by general practitioners (GPs) and/or specialists. Therefore, this study examined asthma management in patients exclusively supervised by specialists (SPE), GPs, (GP) and both (GP+SPE group), and compared the findings. Asthma patients were consecutively recruited in 348 pharmacies. Each patient completed a questionnaire providing data on personal characteristics, asthma management, perception of disease and asthma supervision. Asthma control was measured using the Asthma Control Test. Questionnaires were linked to computerised records of medications which had been dispensed before inclusion in the study. From the 1,256 patients (mean age = 36.1 yrs, 54.3% females), 11.4, 36.6, and 52.0% were placed in the SPE, GP, and GP+SPE groups, respectively. During the previous 4 weeks, most patients in the SPE group were properly controlled (52.2 versus 26.4 and 21.5% in GP and GP+SPE groups, respectively). The SPE group made more use of fixed combinations of long-acting beta agonist and inhaled corticosteroid, while receiving less short-acting beta agonists, antitussives and antibiotics. Striking differences in symptoms and asthma management were observed according to the type of asthma supervision. The current results strongly support the need to improve the management of asthma in primary care, and the coordination of care between general practitioners and specialists.

Adult↗
PubMed2005

Elevated MMP-12 protein levels in induced sputum from patients with COPD.

BACKGROUND: Several matrix metalloproteinases (MMPs) are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). In mice, MMP-12 plays a crucial role in the development of cigarette smoke induced emphysema. A study was undertaken to investigate the role of MMP-12 in the development of COPD in human smokers. METHODS: Induced sputum samples were collected from patients with stable COPD (n = 28), healthy smokers (n = 14), never smokers (n = 20), and former smokers (n = 14). MMP-12 protein levels in induced sputum were determined by ELISA and compared between the four study groups. MMP-12 enzymatic activity in induced sputum was evaluated by casein zymography and by cleaving of a fluorescence quenched substrate. RESULTS: Median (IQR) MMP-12 levels were significantly higher in COPD patients than in healthy smokers, never smokers, and former smokers (17.5 (7.1-42.1) v 6.7 (3.9-10.4) v 4.2 (2.4-11.3) v 6.1 (4.5-7.6) ng/ml, p = 0.0002). MMP-12 enzymatic activity was significantly higher in patients with COPD than in controls (4.11 (1.4-8.0) v 0.14 (0.1-0.2) microg/microl, p = 0.0002). CONCLUSION: MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP-12 in the development of COPD in smokers.

Aged↗
PubMed2005

[Aspergillus bronchitis and aspergilloma treated successfully with voriconazole].

INTRODUCTION: Aspergillus fumigatus is a ubiquitous soil-dwelling organism, which can cause both aspergillomas which develop in a preformed lung cavity, and aspergillus bronchitis. The two pathologies can occasionally co-exist, notably in patients with of cystic fibrosis. CASE REPORT: We describe a 57 year old patient, with diffuse bronchiectasis, who developed aspergillus bronchitis as well as an aspergilloma complicating a cavity caused by an atypical mycobacterial infection. After one month of therapy with voriconazole the aspergilloma had decreased in size and the endobronchial changes had resolved. CONCLUSION: This case report illustrates that in addition to its established role for the treatment of invasive aspergillosis, voriconazole is a promising new therapy for the treatment of aspergilloma and aspergillus bronchitis.

Antifungal Agents↗
PubMed2005

Quality of asthma care: results from a community pharmacy based survey.

BACKGROUND: Optimal control is a major objective of disease management of asthma. The aim of the present study was to provide descriptive data on disease management in asthma patients, including medical resource utilization. METHODS: Asthma patients (age 18-50 years) were consecutively recruited in 348 dispensing pharmacies. They completed a questionnaire which collected data on personal characteristics, asthma management, including medical resource utilization, including asthma management. Asthma control was measured with the Asthma Control Test. Data from computerized pharmacy records of medications, dispensed before inclusion, were also collected. RESULTS: In 1791 eligible patients, 1559 accepted to participate in the study (mean age = 36.5, 56.1% of females). During the previous 4 weeks, the asthma control was satisfactory for only 28% of the patients, despite extensive provision of anti-inflammatory asthma control treatments (89%). Combinations of long acting beta agonists (LABA) and inhaled corticosteroids (ICS) were commonly used (59%), while fewer patients received LABA and ICS as two separate medications (15%). In addition, short-acting beta agonists, were frequently dispensed (71%). A substantial number of patients consulted their GPs on a monthly basis. Patients commonly reported daily shortness of breath (30%), daily use of rescue medication (29%) and weekly nocturnal symptoms (32%). Surprisingly, most patients considered their asthma as completely or well controlled (76%). CONCLUSIONS: Our results clearly identify a need to improve the management of asthma. Education programmes would be beneficial to improve asthma control.

Adolescent↗
PubMed2001

Effect of crown ethers on structure, stability, activity, and enantioselectivity of subtilisin Carlsberg in organic solvents.

Colyophilization or codrying of subtilisin Carlsberg with the crown ethers 18-crown-6, 15-crown-5, and 12-crown-4 substantially improved enzyme activity in THF, acetonitrile, and 1,4-dioxane in the transesterification reactions of N-acetyl-L-phenylalanine ethylester and 1-propanol and that of (+/-)-1-phenylethanol and vinylbutyrate. The acceleration of the initial rate, V(0), ranged from less than 10-fold to more than 100-fold. All crown ethers activated subtilisin substantially, which excludes a specific macrocyclic effect from being responsible. The secondary structure of subtilisin was studied by Fourier-transform infrared (FTIR) spectroscopy. 18-Crown-6 and 15-crown-5 led to a more nativelike structure of subtilisin in the organic solvents employed when compared with that of the dehydrated enzyme obtained from buffer alone. However, the high level of activation with 12-crown-4 where this effect was not observed excluded overall structural preservation from being the primary cause of the observed enzyme activation. The conformational mobility of subtilisin was investigated by performing thermal denaturation experiments in 1,4-dioxane. Although only a small effect of temperature on subtilisin structure was observed for the samples prepared with or without 12-crown-4, both 18-crown-6 and 15-crown-5 caused the enzyme to denature at quite low temperatures (38 degrees C and 56 degrees C, respectively). No relationship between this property and V(0) was evident, but increased conformational mobility of the protein decreased its storage stability. The possibility of a "molecular imprinting" effect was also tested by removing 18-crown-6 from the subtilisin-18-crown-6 colyophilizate by washing. V(0) was only halved as a result of this procedure, an effect insignificant compared with the ca. 80-fold rate enhancement observed prior to washing in THF. This suggests that molecular imprinting is likely the primary cause of subtilisin activation by crown ethers, as recently suggested.

Acetonitriles↗
PubMed2001

[Neoadjuvant chemoradiotherapy and peroperative radiotherapy for non-small-cell lung cancer of the apex. A study of 5 cases].

The management of superior sulcus tumors with Pancoast 's syndrome is not well defined, especially in view of their low frequency. Even if surgery performed by "en bloc" resection of the tumor and the chest wall is recommended, neoadjuvant treatment could have a potential benefit on the resecability and pain control. We report five cases of Pancoast tumors (NSCLC), treated by radiotherapy and chemotherapy before surgery. Four tumors was on stage IIIb. A regimen with radiotherapy (50 Gy) and chemotherapy (cisplatinum + etoposide) was initially performed. Four tumors were resected, with 2 complete pathologic responses and good control on pain. Three patients received radiotherapy during surgery. No toxic reaction was observed. This regimen may be discussed with locally advanced tumors and poor prognosis.

Aged↗
PubMed2000

Genome screen for asthma and related phenotypes in the French EGEA study.

A genome-wide search was conducted in 107 nuclear families with at least two siblings with asthma, as part of the French EGEA study. A two-stage analysis strategy was applied to the 107 families divided into two independent subsets of 46 and 61 families, where all regions detected in the first set of families were tested for replication in the second set. In addition, all regions reported by published genome scans in different populations were examined in the total sample. A total of 254 markers were typed in the first set of families and 70% of them in the second set. Linkage was investigated by model-free methods for asthma and four asthma-related phenotypes: bronchial responsiveness (BR), skin test response, total immunoglobulin E (IgE) levels, and eosinophil count. The two-stage analysis led to the detection of three regions: 11p13 for IgE, 12q24 for eosinophils, and 17q12-21 for asthma and skin tests. Among the regions reported by published genome screens, seven were found in the 107 French EGEA families: three being already detected by the two-stage analysis, 11p13 (p = 0.005), 12q24 (p = 0.0008), and 17q12-21 (p = 0.001), and four additional ones, 1p31 (p = 0.005) for asthma, 11q13 (p = 0.006) for IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.

Adolescent↗
PubMed2000

[Respiratory manifestations after exposure to sulfurous anhydride in wine-cellar workers: 6 case reports].

Sulfite treatment of wine [a process exploiting the biocidal and anti-oxidant properties of sulfur dioxide (SO2)] involves the use of liquified gas, aqueous solutions or bisulfites, i.e. the salts of sulfurous acid which slowly release SO2. This procedure can result in repeated exposures of operators to significant amounts of SO2. However, risks associated with the use of SO2 are greatly under-estimated by wine producers and wine-cellar workers. We report on 6 cases of respiratory symptoms attributable to SO2 identified during a survey of wine-cellars in the French Beaujolais district. Their pathogenesis is discussed after an overview of the occupational toxicology of SO2.

Adult↗
PubMed2000

[Digestive disorders and Legionnaires' lung disease. Accompanying signs or visceral location?].

Digestive disorders in Legionella pneumophila pneumonia such as nausea, vomiting, diarrhoea, are common; they are clinical arguments to suspect this bacteria to be responsible for this pneumonia. In this case-report, a patient with pneumonia due to Legionella pneumophila serogroup I presented in the follow-up with signs of enteritis with ascites. We looked ahead in literature who made us discover the multiple organ involvement that may happen in Legionnaires' disease. Diagnostic procedures consist in simple tests as ultrasonography, abdominal computerised tomography, that show inflammatory disease signs and sometimes ascites. Exceptionally, Legionella pneumophila has been demonstrated with direct immunofluorescent microscopic study, in inflammatory colitis pieces with haemorrhagic necrosis in different stage processes. Pathogenesis could be explained by the systemic spread of the organism and formation at distance of necrotising enteritis focus. It is initiated by necrotising factors of bacterial origin and hypersensitivity reactions (type I and III).

Adult↗
PubMed2000

Pulmonary mucormycosis in a diabetic patient.

We present the case of a 54 year-old male from Moldavia with diabetes mellitus (type II diabetic), admitted to hospital in January 1999, with ketoacidosis and consolidation of the lower left lobe. The diagnosis of mucormycosis was confirmed by identification of large, nonseptate hyphae of the order Mucorales. A strain of Rhizopus oryzae (Rhizopus arrhizus) was isolated from culture on sabouraud medium. The patient was treated by systemic amphotericin B, associated with surgical debridement (lobectomy). The treatment with amphotericin B was stopped after ten days and the patient was completely asymptomatic and returned to Moldavia. Mucormycoses are rare, and tend to be encountered in individuals with predisposing factors such as malignant blood disorders (immunocompromised patients) or diabetes mellitus. Prognosis is poor, resembling infection with Aspergillus, despite aggressive treatment as in the present case. The gravity of the condition can be accounted for by the thrombotic and necrosing nature of the fungal invasion of lung vessels.

Diabetes Complications↗
PubMed1999

CD40 expression by human bronchial epithelial cells.

CD40 is a 50-kDa protein expressed on B cells, dendritic cells, monocytes and epithelial cells, but the distribution of CD40 expression in humans is not completely known. It binds to a ligand (CD40L) which is expressed essentially on activated T cells. The interaction between CD40 and CD40L plays important roles in immune responses. CD40 expression was investigated on bronchial tissues and human bronchial cell lines using immunohistochemistry, immunofluorescence staining and analysis with a cytometer, respectively. Constitutive CD40 expression, but not that of CD40L, was slightly detectable on normal human bronchial epithelial cells (HBEC) in situ and on an adult lung adenocarcinoma (SKLU1) cell line, while another cell line, a bronchial transformed SV40 cell line (WI26VA4), was negative for CD40. Among the various cytokines tested, only interferon (IFN)-gamma was found to induce CD40 expression on WI26VA4. Tumour necrosis factor (TNF)-alpha was the best cytokine able to up-regulate CD40 in SKLU1 cells. A combination of IFN-gamma and TNF-alpha was slightly more effective than the cytokine alone at up-regulating CD40 expression on both cell lines. We further investigated the functional consequences of CD40 ligation on both cell lines. These bronchial cells expressed CD40, HLADR and CD54 under basal conditions or when stimulated by cytokines. Stimulation through CD40 did not affect cell-surface-antigen expression on either cell line. The production of cytokines such as interleukin (IL)-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) by HBEC has been described. SKLU1 and WI26VA4 cells released IL-6 and GM-CSF spontaneously. Whatever the case, CD40 engagement did not modulate spontaneous or TNF-alpha-induced production of these two cytokines. These data indicate for the first time that normal HBEC express CD40 in situ. Further investigations are required in order to determine the role of CD40 on normal HBEC.

Bronchi↗
PubMed1999

Fas and Fas ligand expression in cystic fibrosis airway epithelium.

BACKGROUND: Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defective expression of CFTR protein in epithelial cells. The main cause of mortality in CF is linked to chronic inflammatory and infectious airway processes. Recent studies have suggested perturbations in the apoptotic process in CF cell lines and enterocytes. A study was undertaken to investigate the expression of Fas and Fas ligand (FasL) in CF bronchial epithelium and CF tracheal cell lines. METHODS: Immunohistochemical staining for Fas (alkaline phosphatase anti-alkaline phosphatase) and FasL (immunoperoxidase) was performed in eight CF bronchial epithelial samples and four controls and immunohistochemical DNA fragmentation (TUNEL) was carried out in four CF patients and four controls. Immunofluorescence staining and flow cytometric analysis of Fas and FasL expression was performed in two human tracheal epithelial cell lines (HTEC) with normal and CF genotype. The dosage of serum soluble FasL was examined in 21 patients with CF and 14 healthy volunteers. RESULTS: FasL expression was markedly increased in patients with CF in both the ciliated and submucosal glandular bronchial epithelium compared with controls; Fas was similarly expressed in bronchial samples from controls and CF patients in both the ciliated epithelium and submucosal glands. High levels of DNA fragmentation were observed in CF but with some epithelial cell alterations. Serum concentrations of soluble FasL were frequently undetectable in patients with CF. In vitro, HTEC expressed Fas and FasL in both genotypes. A higher mean fluorescence intensity for FasL expression was noted in CF genotype HTEC with median (range) for six experiments of 74 (25-101) for CF cells and 42 (21-70) for non-CF cells. CONCLUSION: Fas/FasL interaction is probably implicated in the human CF airway apoptotic pathway. The mechanisms of induction of FasL expression and its role in inducing tissue damage or remodelling or in controlling local inflammatory cell apoptosis remain to be determined.

Adolescent↗
PubMed1999

[Biological diagnosis of immediate drug allergy. Comparative study of histamine liberation tests and CD63 expression by flow cytometry (preliminary results)].

The diagnosis of drug allergy is mainly based upon a detailed clinical history, positive skin tests (ST) and detection of specific IgE. In case of discrepant results, in vitro investigations to identify the responsible drug are needed. The histamine release test (HR) is usually performed. Nevertheless, its clinical benefit remains controversial. Flow cytometric methods (FCM) for the study of allergen induced basophil activation have been recently described. We assessed their usefulness in the diagnosis of drug allergy in comparison to HR results. Eighteen patients were included and 24 drugs (mainly antibiotics and muscle relaxant drugs) were tested. On the basis of clinical signs, 15 patients were classified as allergic (18 drugs). Sensitivity of biological investigations were found as follows: 71% (ST), 71% (FCM) and 24% (HR). This suggests performing FCM rather than HR. In addition, HR is more costly in terms of both reagents and laboratory technician time. Thus, CD63 detection by FCM seems to be a more reliable method in the clinical immunology laboratory. Additional data are needed to validate these preliminary results (sensitivity and specificity, especially in atopic patients) and to assess the interest of the method to investigate drug allergy due to other types of molecules.

Antigens, CD↗
PubMed1999

[Patient knowledge of asthma: results of a national survey in pneumology].

Knowledge of asthma and its treatment were evaluated in a survey of 1,000 asthmatics using a self-questionnaire with closed questions. As far as the disease was concerned, 87.4% of patients knew that the bronchi were the pathological organ and 70.6% that the disease persisted between attacks. Overall knowledge of the disease (pathological organ, persistence of the disease between attacks, chronic inflammation associated with acute bronchoconstriction) was adequate in only 25.6% of patients. It was associated with the educational level [higher > primary; p = 0.001], the grade of asthma [severe > mild; p = 0.007] and the number of medicines inhaled [(n > 3) > (N < 2); p = 0.001)]. As far as medicines were concerned, knowledge of their mechanisms of action varied according to therapeutic groups: antiallergics [78.6%], antibiotics [77.7%], antihistamines [74.5%], LA beta2-mimetics [45.9%], theophylline [31.9%], corticosteroids [31.7%], beta2-mimetics [24.8%]. No factor was statistically correlated with greater familiarity. However, only 7.2% of patients treated with metered-dose aerosols expressed handling problems and 78.8% of asthmatics questioned felt that they were sufficiently informed about their disease and its treatment. Information and education thus remain a priority in the management of asthma.

Adolescent↗
PubMed1998

Subepithelial fibrosis and degradation of the bronchial extracellular matrix in cystic fibrosis.

Cystic fibrosis is a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator gene. Chronic inflammation and proteolysis lead to progressive damage of the bronchial wall. Extracellular matrix determines the structural organization and the mechanical properties of lung airways. It was thus examined in nine patients with cystic fibrosis (six bronchial biopsies and three lobectomies) in order to assess its level of alteration. The submucosal changes in matrix protein distribution were analyzed by immunochemistry and electron microscopy: the subepithelial basal lamina was thinned; an acellular collagen fiber layer composed of interstitial collagens (types I and III) subtended by tenascin and devoid of elastin-associated microfibrils was deposited beneath the basal lamina; this dense fibrous deposit generally formed a thick layer and could extend into the bronchial wall; the bronchial elastic framework lost arborescent distribution and appeared slender, packed, or lacunar; ultrastructural observation gave evidence for elastic and collagenic fiber lysis. Proteolytic activity is probably the major cause of matrix degradation. Fibrosis appears as a repair process rather than as an active fibrogenesis. The reversibility of extracellular matrix alterations is an important challenge and various interventions such as anti-inflammatory treatments can be targeted to halt or reverse this degradation process.

Adolescent↗
PubMed1997

Correlation between arachidonic acid oxygenation and luminol-induced chemiluminescence in neutrophils: inhibition by diethyldithiocarbamate.

Neutrophils from allergic subjects were hypersensitive to stimulation by low calcium ionophore concentration (0.15 microM), resulting in an increased formation of leukotriene B4 (LTB4), 5S-hydroxy-6,8,11,14-(E,Z,Z,Z)-eicosatetraenoic acid (5-HETE), and other arachidonic acid metabolites through the 5-lipoxygenase pathway. In parallel, luminol-dependent chemiluminescence was also higher in neutrophils from allergic patients at the basal state and after stimulation by calcium ionophore, revealing an enhancement of radical oxygen species and peroxide production. The activity of glutathione peroxidase, the main enzyme responsible for hydroperoxide reduction, was lowered in these cells. Diethyl-dithiocarbamate (DTC) induced a concentration-dependent decrease in chemiluminescence and arachidonic acid metabolism after neutrophil stimulation. These data show that the elevation of arachidonic acid metabolism in neutrophils from allergic patients is strongly correlated with oxidative status. This elevation may be the consequence of an increased cellular hydroperoxide known to activate 5-lipoxygenase (5-LOX) activity and/or an increased arachidonic acid availability, due either to phospholipase A2 (PLA2) activation or inhibition of arachidonate reesterification into phospholipids. Lowering this oxidative status was associated with a concomitant decrease of this metabolism. Our results suggest that the effect of DTC may be the consequence of an inhibition of peroxyl radical and cellular lipid hydroperoxide production. Thus, DTC may modulate arachidonic acid metabolism in neutrophils by modulating the cellular hydroperoxide level.

Adult↗