Chromosomal bands affected by acute oil exposure and DNA repair errors.

BACKGROUND: In a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk. OBJECTIVES: We analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency. METHODS: Cytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin. RESULTS: Three chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016). CONCLUSION: The present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas) reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure.

Carcinoide bronquial y síndrome de neoplasias endocrinas múltiples TIPO 1. Aportación de un caso / Bronchial Carcinoid and Type 1 Multiple Endocrine Neoplasia Syndrome. A case report

Los tumores carcinoides de origen bronquial son raros en el síndrome de neoplasias endocrinas múltiples tipo 1 (MEN1). La prevalencia de casos con confirmación histológica es aproximadamente del 5%–8%, aunque en estudios más recientes se estima que podría ser más alta y, en ellos, se contempla una posible relación con la presencia de hipergastrinemía. Aportamos una paciente con síndrome de MEN1, sin síntomas respiratorios, con hipergastrinémia, y que en una tomografía computarizada se detectó un nódulo de 5mm de diámetro en la pared del bronquio principal izquierdo. La biopsia bronquial confirmó que se trataba de un carcinoide bronquial típico y el Octeoscran® mostró un único foco de hipercaptación coincidente con esta lesión. Se realizó una broncotomía con extirpación de 3 anillos bronquiales, que también demostró que se trataba de un carcinoide típico(AU)

Carcinoid tumours of bronchial origin are rare in type 1 multiple endocrine neoplasia (MEN1) syndrome. The prevalence of histologically confirmed cases is approximately 5–8%, although in more recent studies it is estimated that it could be much higher and a possible relationship with the presence of hypergastrinaemia is suggested. We report a patient with a type 1 MEN syndrome, with no respiratory symptoms, with hypergastrinaemia, and in whom a 5mm diameter nodule was detected in the wall of the left main bronchus by computed tomography. The bronchial biopsy confirmed that it was a typical bronchial carcinoid and the octreoscan showed a single focus of high uptake coinciding with this lesion. A bronchoplastic (sleeve) was performed with extirpation of 3 bronchial rings, which also demonstrated that it was a typical carcinoid(AU)

Health changes in fishermen 2 years after clean-up of the Prestige oil spill.

BACKGROUND: In 2002, the oil tanker Prestige spilled more than 67,000 tons of bunker oil, heavily contaminating the coast of northwestern Spain. OBJECTIVE: To assess respiratory effects and chromosomal damage in clean-up workers of the oil spill 2 years after the exposure. DESIGN: Cross-sectional study. SETTING: Fishermen cooperatives in coastal villages. PARTICIPANTS: Local fishermen who were highly exposed (n = 501) or not exposed (n = 177) to oil 2 years after the spill. MEASUREMENTS: Respiratory symptoms; forced spirometry; methacholine challenge; markers of oxidative stress (8-isoprostane), airway inflammation (interleukins, tumor necrosis factor-α, and interferon-γ), and growth factor activity in exhaled breath condensate; and chromosomal lesions and structural alterations in circulating lymphocytes. RESULTS: Compared with nonexposed participants, persons exposed to oil were at increased risk for lower respiratory tract symptoms (risk difference, 8.0 [95% CI, 1.1 to 14.8]). Lung function did not significantly differ between the groups. Among nonsmoking participants, exposed individuals had higher exhaled 8-isoprostane levels than nonexposed individuals (geometric mean ratio, 2.5 [CI, 1.7 to 3.7]), and exposed individuals with lower respiratory tract symptoms had higher 8-isoprostane levels than those of exposed individuals without symptoms. Exposed nonsmoking participants also had higher levels of exhaled vascular endothelial growth factor (risk difference, 44.8 [CI, 27.9 to 61.6]) and basic fibroblast growth factor (risk difference, 16.0 [CI, 3.5 to 28.6]). A higher proportion of exposed participants had structural chromosomal alterations (risk difference, 27.4 [CI, 10.0 to 44.8]), predominantly unbalanced alterations. The risk for elevated levels of exhaled 8-isoprostane, vascular endothelial growth factor, and basic fibroblast growth factor and structural chromosomal alterations seemed to increase with intensity of exposure to clean-up work. LIMITATIONS: The clinical significance of exhaled biomarkers and chromosomal findings are uncertain. The association between oil exposure and the observed changes may not be causal. The findings may not apply to spills involving other types of oil or to different populations of oil spill workers. CONCLUSION: Participation in clean-up of a major oil spill was associated with persistent respiratory symptoms, elevated markers of airway injury in breath condensate, and chromosomal damage.

[Bronchial carcinoid and type 1 multiple endocrine neoplasia syndrome. A case report]. / Carcinoide bronquial y síndrome de neoplasias endocrinas múltiples TIPO 1. Aportación de un caso.

Carcinoid tumours of bronchial origin are rare in type 1 multiple endocrine neoplasia (MEN1) syndrome. The prevalence of histologically confirmed cases is approximately 5-8%, although in more recent studies it is estimated that it could be much higher and a possible relationship with the presence of hypergastrinaemia is suggested. We report a patient with a type 1 MEN syndrome, with no respiratory symptoms, with hypergastrinaemia, and in whom a 5mm diameter nodule was detected in the wall of the left main bronchus by computed tomography. The bronchial biopsy confirmed that it was a typical bronchial carcinoid and the octreoscan showed a single focus of high uptake coinciding with this lesion. A bronchoplastic (sleeve) was performed with extirpation of 3 bronchial rings, which also demonstrated that it was a typical carcinoid.

Tratamiento endoscópico de metástasis en bronquios principales de sarcoma: aportación de 2 casos / Endoscopic treatment of metastasis in the main bronchi from sarcoma: a report of 2 cases

El leiomiosarcoma es un tumor que puede localizarse en tejidos blandos o en órganos. El tratamiento consiste en la resección quirúrgica completa del tumor. El pronóstico es difícil de predecir y después de un largo período sin enfermedad pueden aparecer metástasis a distancia. Las metástasis pulmonares son frecuentes, pero su localización en bronquios principales con atelectasia pulmonar es muy rara. Presentamos 2 casos de atelectasia pulmonar y neumonitis obstructiva secundaria a metástasis en bronquios principales de un leiomiosarcoma de útero y de un leiomiosarcoma de muslo, respectivamente, que tratamos con resección endoscópica. Analizamos el papel del tratamiento endoscópico con láser para paliar los síntomas y como ayuda previa a la realización de otro tipo de tratamiento oncológico(AU)

Leiomyosarcoma is a cancer that can affect the soft tissues or organs. The standard treatment is complete tumor resection. Prognosis is difficult to predict and distant metastases can occur after a long disease-free period. Lung metastases are common but metastasis to the main bronchi with pulmonary atelectasis is very rare. We describe 2 cases of pulmonary atelectasis and obstructive pneumonitis due to metastasis to the main bronchi from leiomyosarcoma of the uterus in one of the patients and leiomyosarcoma of the thigh in the other. Both patients were treated with endoscopic resection. We discuss the role of endoscopic laser treatment in the palliation of symptoms and as an initial procedure before other cancer treatments are started(AU)

[Endoscopic treatment of metastasis in the main bronchi from sarcoma: a report of 2 cases]. / Tratamiento endoscópico de metástasis en bronquios principales de sarcoma: aportación de 2 casos.

Leiomyosarcoma is a cancer that can affect the soft tissues or organs. The standard treatment is complete tumor resection. Prognosis is difficult to predict and distant metastases can occur after a long disease-free period. Lung metastases are common but metastasis to the main bronchi with pulmonary atelectasis is very rare. We describe 2 cases of pulmonary atelectasis and obstructive pneumonitis due to metastasis to the main bronchi from leiomyosarcoma of the uterus in one of the patients and leiomyosarcoma of the thigh in the other. Both patients were treated with endoscopic resection. We discuss the role of endoscopic laser treatment in the palliation of symptoms and as an initial procedure before other cancer treatments are started.

Plasmocitoma pulmonar primario: aportación de 3 casos / Three Cases of Primary Pulmonary Plasmacytoma

El plasmocitoma extramedular es un tumor de células plasmáticas que es más frecuente en el aparato respiratorio superior. La localización pulmonar es rara y puede presentarse como enfermedad limitada al pulmón y ganglios regionales, o bien como enfermedad diseminada. Cuando se localiza sólo en el aparato respiratorio inferior (plasmocitoma pulmonar primario), el diagnóstico es difícil y generalmente se realiza en la pieza quirúrgica. Aportamos 3 casos, con la peculiaridad en 2 de ellos de que el diagnóstico se confirmó mediante biopsia bronquial. Otros datos relevantes son la presencia de paraproteína en sangre y orina en 2 de los casos, y el seguimiento durante 10 y 15 años sin recidiva de la enfermedad(AU)

Extramedullary plasmacytoma is a plasma cell malignancy that most commonly occurs in the upper respiratory tract. Plasmocytoma located in the lung is an unusual finding, and in such cases the disease may be confined to the lung and regional lymph nodes or may be disseminated. When only located in the lower respiratory tract (primary pulmonary plasmacytoma), diagnosis is difficult and is usually based on the excised tissue. We present 3 cases, 2 of which were particularly unusual in that diagnosis was confirmed by bronchial biopsy. Other important findings included the detection of paraprotein in the blood and urine of 2 of the patients, and follow-ups over 10 and 15 years without recurrence of the disease in 2 of the cases(AU)

Desarrollo de un modelo murino de inflamación y remodelación de vías respiratorias en asma experimental / Development of a Murine Model of Airway Inflammation and Remodeling in Experimental Asthma

IntroducciónLa investigación de los mecanismos de enfermedad del asma y la identificación de nuevas dianas terapéuticas requieren modelos animales experimentales. En este trabajo presentamos los datos del desarrollo de un modelo murino de asma experimental que permite valorar de forma conjunta parámetros de inflamación y remodelación de las vías respiratorias mediante morfología cuantitativa.Material y métodosSe sensibilizó a ovoalbúmina a ratones Balb/c y se les realizó broncoprovocación con ovoalbúmina o excipiente 3 veces por semana durante 12 semanas.ResultadosEn el lavado broncoalveolar, los ratones del grupo de ovoalbúmina presentaron un incremento significativo de leucocitos totales, con una mediana (cuartiles 25–75) de 670,0células/ml·103 (376,2–952,5), frente a 40,0células/ml·103 (60,0–85,0) en controles (p=0,001), y de las fracciones eosinófila y linfocitaria en recuento diferencial. En secciones sagitales de los pulmones inflados a presión estandarizada, estos ratones mostraron hiperplasia de células caliciformes en el epitelio respiratorio —reacción de ácido peryódico de Schiff: 53,89 (36,26–62,84) frente a 0,66 (0,00–1,06)células/mm2 (p<0,001)—, densa infiltración inflamatoria mononuclear y eosinófila —hematoxilina-eosina: 32,87 (27,34–37,13) frente a 0,06 (0,00–0,20)eosinófilos/mm2 (p=0,002)—, infiltración subepitelial por mastocitos —azul de toluidina: 2,88 (2,00–3,28) frente a 0,28 (0,15–0,35)mastocitos/mm2 (p<0,001)—, incremento de la masa de tejido contráctil —inmunofluorescencia para alfaactina de músculo liso: 2,60 (2,28–2,98) frente a 1,08 (0,93–1,16), adimensional (p<0,001)— e incremento del depósito de matriz extracelular (tricrómico de Masson: 2,18 (1,85–2,80) frente a 0,50 (0,37–0,65), adimensional (p<0,001)—.ConclusionesLos datos aportados configuran un modelo de asma experimental inducida por exposición alergénica prolongada, con desarrollo y evaluación integrada de inflamación y remodelación de vías respiratorias(AU)

Background and ObjectiveExperimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling.Material and MethodsBALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks.ResultsOn bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25–Q75) of 670.0cells/mL×103 (376.2, 952.5) in comparison with 40.0cells/mL×103 (60.0–85.0) in controls (P=.001), and higher eosinophil and differential lymphocyte counts. In sagittal sections of lungs inflated to a standard pressure, the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium (periodic acid-Schiff staining, 53.89 [36.26–62.84]cells/mm2 vs 0.66 [0.00–1.06]cells/mm2, P<.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34–37.13]eosinophils/mm2 vs 0.06 [0.00–0.20]eosinophils/mm2, P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00–3.28] mast cells/mm2 vs 0.28 [0.15–0.35] mast cells/mm2, P<.001), increased contractile tissue mass (immunofluorescence analysis for α-smooth-muscle actin, 2.60 [2.28–2.98] vs 1.08 [0.93–1.16], dimensionless, P<.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85–2.80] vs 0.50 [0.37–0.65], dimensionless, P<.001).ConclusionsOur dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together(AU)

[Three cases of primary pulmonary plasmacytoma]. / Plasmocitoma pulmonar primario: aportación de 3 casos.

Extramedullary plasmacytoma is a plasma cell malignancy that most commonly occurs in the upper respiratory tract. Plasmocytoma located in the lung is an unusual finding, and in such cases the disease may be confined to the lung and regional lymph nodes or may be disseminated. When only located in the lower respiratory tract (primary pulmonary plasmacytoma), diagnosis is difficult and is usually based on the excised tissue. We present 3 cases, 2 of which were particularly unusual in that diagnosis was confirmed by bronchial biopsy. Other important findings included the detection of paraprotein in the blood and urine of 2 of the patients, and follow-ups over 10 and 15 years without recurrence of the disease in 2 of the cases.

[Development of a murine model of airway inflammation and remodeling in experimental asthma]. / Desarrollo de un modelo murino de inflamación y remodelación de vías respiratorias en asma experimental.

BACKGROUND AND OBJECTIVE: Experimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling. MATERIAL AND METHODS: BALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks. RESULTS: On bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25-Q75) of 670.0 cells/mL x 10(3) (376.2, 952.5) in comparison with 40.0 cells/mL x 10(3) (60.0-85.0) in controls (P=.001), and higher eosinophil and differential lymphocyte counts. In sagittal sections of lungs inflated to a standard pressure, the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium (periodic acid-Schiff staining, 53.89 [36.26-62.84]cells/mm(2) vs 0.66 [0.00-1.06]cells/mm(2), P<.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34-37.13]eosinophils/mm(2) vs 0.06 [0.00-0.20]eosinophils/mm(2), P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00-3.28] mast cells/mm(2) vs 0.28 [0.15-0.35] mast cells/mm(2), P<.001), increased contractile tissue mass (immunofluorescence analysis for alpha-smooth-muscle actin, 2.60 [2.28-2.98] vs 1.08 [0.93-1.16], dimensionless, P<.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85-2.80] vs 0.50 [0.37-0.65], dimensionless, P<.001). CONCLUSIONS: Our dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together.

Prolonged respiratory symptoms in clean-up workers of the prestige oil spill.

RATIONALE: The wreckage of the oil tanker Prestige in November 2002 produced heavy contamination off the coast of Galicia, Spain. OBJECTIVES: To evaluate the prevalence of respiratory symptoms in local fishermen more than 1 year after having participated in clean-up work. METHODS: Questionnaires including qualitative and quantitative information about clean-up activities and respiratory symptoms were distributed among associates of 38 fishermen's cooperatives. Both postal and telephone follow-up was performed. The association between participation in clean-up work and respiratory symptoms was evaluated using multiple logistic regression analyses, adjusted for sex, age, and smoking status. MEASUREMENTS AND MAIN RESULTS: Between January 2004 and February 2005, data were obtained from 6,780 fishermen (response rate, 76%). Sixty-three percent had participated in clean-up operations. Lower respiratory tract symptoms (LRTS) were more prevalent in clean-up workers: odds ratio (OR), 1.73; 95% confidence interval (CI), 1.54-1.94. This association was consistent for men and women, for different fishermen's cooperatives, and for different types of respiratory symptoms, and remained after excluding those who reported anxiety or believed that the oil spill had affected their health (OR, 1.57; 95% CI, 1.37-1.80). The risk of LRTS increased with the number of exposed days, exposed hours per day, and number of activities (linear trend, P < 0.0001). The excess risk of LRTS decreased when more time had elapsed since last exposure: OR, 2.33, 1.69, and 1.24 for less than 14 months, 14-20 months, and more than 20 months, respectively. CONCLUSIONS: Participation in clean-up work of oil spills may result in prolonged respiratory symptoms that last 1 to 2 years after exposure.

Prescription of oral corticosteroids in near-fatal asthma patients: relationship with panic-fear, anxiety and depression.

Oral corticosteroids are the most effective drugs for illness management, especially in near-fatal asthma (NFA) patients. Prescription of oral corticosteroids in other groups of asthmatic patients has been shown to be related not only to clinical features of the illness, but also to psychological variables, what suggests the need to investigate this relationship specifically in NFA patients. Forty-two NFA patients aged 18--83 were interviewed to collect data on sociodemographics, clinical features and psychological variables, specifically panic-fear, anxiety and depression; 45.2% had been prescribed oral corticosteroids and 54.8% had not been prescribed this type of medication. Only frequency and severity of symptoms (odds ratio=3.14; 95% confidence interval=1.27-7.79; p=0.013) and state-anxiety (odds ratio=1.03; 95% confidence interval=1.03-1.29; p=0.015) emerged as significant risk indicators for the prescription of oral corticosteroids. These preliminary results in NFA patients confirm previous reports about the relationship between prescription of oral corticosteroids and psychological variables in asthmatic patients. State-anxiety could increase the magnitude of breathing difficulties, and thus imply the need for more effective medications for its management, but further research is necessary to reject other possible explanations.

Bronquiolitis obliterante con neumonía organizativa y cirrosis biliar primaria / Bronchiolitis obliterans with organizing pneumonia and primary biliary cirrhosis

No disponible

Speed of recovery from acute exacerbations of chronic obstructive pulmonary disease after treatment with antimicrobials : results of a two-year study.

OBJECTIVE: We performed a multicentre study under a 2-year observational protocol that included data on time to recovery from acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) in patients receiving moxifloxacin and comparator antimicrobials. PATIENTS AND METHODS: Outpatients with moderate or severe COPD were recruited from respiratory clinics throughout Spain. Moxifloxacin was available in year 2, and was to be prescribed to 50% of patients in that period in a non-randomised allocation. Time to recovery was compared in successfully treated AE-COPD; cross-sectionally for all AE-COPD over 2 years, first AE-COPD and all AE-COPD in year 2, and longitudinally in patients receiving comparator antimicrobials for AE-COPD in year 1 and moxifloxacin in year 2. RESULTS: 614 AE-COPD were treated in 441 patients over 2 years (mean age 66.7 +/- 8.3 years, 98% males, mean forced expiratory volume in 1 second [FEV(1)] 35.9 +/- 8.8%). Mean time to recovery overall was 4.6 days (SD 3.3) with moxifloxacin 400 mg/day for 5 days, and 5.8 days (SD 4.6) with comparators (p < 0.01), which were most frequently amoxicillin/clavulanic acid 500/125mg/8h, clarithromycin 500mg/12h and cefuroxime axetil 500mg/12h for 7-10 days. Longitudinal analysis showed that 27 patients treated with moxifloxacin in the second year of the study recovered in a mean of 3.7 days (SD 3.1), and the same patients treated with comparator antimicrobials in year one recovered in a mean of 6.8 days (SD 4.6) [p = 0.02]. In contrast, in 66 patients treated with comparator antimicrobials in both years, mean time to recovery was 7.4 days (SD 7.3) in year one and 5.5 days (SD 3.5) in year two (p = 0.24). All subgroup analyses showed a statistically significant reduction of 18-25% in time to recovery with moxifloxacin compared with other antibiotics. CONCLUSIONS: Moxifloxacin significantly reduced time to recovery from AE-COPD in patients with moderate to severe disease by approximately 20% (>1 day) compared with other antimicrobials. Faster recovery should result in earlier return to work or normal activities, and to social and economic savings.