bluuebunny/crossref_metadata_2025 huggingface dataset:
Deposition of amphotericin B aerosols in pulmonary aspergilloma
Authors: Diot P , Rivoire B , Le Pape A , Lemarie E , Dire D , Furet Y , Breteau M , Smaldone GC
Published: August 2003

The aim of the present study was to characterize amphotericin B aerosols nebulized by ultrasonic and jet nebulizers and to study their deposition and pharmacokinetics in patients with pulmonary mycetoma. The aerodynamic behaviour and pulmonary deposition of amphotericin B particles were measured using a direct isotopic method based on stable labelling of the drug with 99mTc. Each nebulizer was bench tested for inhaled mass and particle size distribution. Three patients suffering from pulmonary aspergilloma were enrolled for a 4 week clinical study. They received 5 mg of amphotericin B daily delivered by either Fisoneb or DP100 (ultrasonic) or Respirgard II (jet) nebulizers. Deposition of radiolabelled amphotericin B was measured once with each nebulizer using a gamma-camera. In two patients, amphotericin B serum concentration was monitored over a 330 min period after the nebulization had been completed. Inhaled masses of the three nebulizers, assessed as % of labelled drug caught in inspiratory filter in duplicate experiments, were: 5.8 and 3.6% for Respirgard II; 26.5 and 28.3% with Fisoneb; 5.9 and 6.3% for DP100. Mass median aerodynamic diameter (mean +/- SD) results were: 0.28 +/- 0.04 micron with Respirgard II; 4.82 +/- 0.78 microns with Fisoneb; and 2.27 +/- 1.14 microns with DP100. Because of larger particles and significantly greater inhaled mass, Fisoneb delivered more amphotericin B to the central airways, the lung periphery and in the mycetoma lung regions. Amphotericin B serum concentrations correlated with pulmonary deposition and remained below 25 ng.mL-1. No untoward effects were reported by the patients during the 4 week trial.(ABSTRACT TRUNCATED AT 250 WORDS)
Decreased lung function in one year survivors of allogeneic bone marrow transplantation conditioned with high-dose busulphan and cyclophosphamide
Authors: Lund MB , Kongerud J , Brinch L , Evensen SA , Boe J
Published: August 2003

Conditioning with busulphan (BU) and cyclophosphamide (CY) prior to allogeneic bone marrow transplantation (BMT) is an alternative to regimens that include total body irradiation (TBI). The aim of the study was to assess the occurrence and degree of lung function impairment after this treatment. Prospectively, 43 consecutive patients, aged 17-51 (median 31) yrs, were examined by lung function measurements and clinical and radiographic evaluation, prior to BMT and at 3 month intervals up to 1 yr after BMT. All patients had normal chest radiographs before BMT and at the 12 month follow-up. Mean baseline values were above 100% of predicted normal for lung volumes and above 90% for gas transfer. Excluded from the lung function follow-up analyses were nine patients who had suffered infectious pneumonia and/or developed obliterative bronchiolitis. For the remaining patients (n = 34), mean alveolar volume (VA), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) had dropped by nearly 10% compared with baseline 3 months after BMT, but were restored within 1 yr. FEV1/FVC x 100 (FEV1%) was increased, reflecting the restrictive pattern. Hb-adjusted transfer factor of the lungs for carbon monoxide (TL,CO) had dropped by 20% after 3 months, and remained reduced by 15% after 1 year. Prior to BMT the smokers had significantly lower TL,CO than the nonsmokers, and after BMT the difference was accentuated. Reductions in lung function were independent of sex, age and type of haematological disorder. We conclude that BMT with BU/CY is associated with transient declines in lung volumes and a persistent reduction in gas transfer 1 yr after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of bronchoalveolar lavage in the diagnosis of fat embolism syndrome
Authors: Roger N , Xaubet A , Agusti C , Zabala E , Ballester E , Torres A , Picado C , Rodriguez-Roisin R
Published: August 2003

Fat embolism syndrome (FES) is a serious clinical disorder occurring in trauma patients. The diagnosis of fat embolism syndrome may be difficult to establish clinically. We therefore wanted to investigate the usefulness of bronchoalveolar lavage (BAL) in the diagnostic evaluation of fat embolism syndrome. We analysed the presence of fat droplets in BAL cells in 32 trauma patients (7 with full diagnostic criteria of fat embolism syndrome, 17 with incomplete diagnostic criteria, and 8 with no diagnostic criteria at the time of bronchoscopy), 9 nontrauma patients with acute respiratory failure and radiographic pulmonary infiltrates, and a control group composed of 10 individuals. An increased percentage of oil red O positive alveolar macrophages (cut-off point > 3%) in BAL was found in 6 out of 7 patients with definite clinical criteria of fat embolism syndrome, and in 6 out of 20 trauma patients without the clinical diagnosis of fat embolism syndrome. In two patients with fat embolism syndrome, sequential BAL showed that the percentage of positive macrophages decreased when the clinical manifestations disappeared. An increased number of BAL macrophages with fat droplets was also observed in two trauma patients without evidence of fat embolism syndrome after long-bone surgical intervention. By contrast, all non-trauma patients had a percentage of positive cells lower than 3%. Our findings suggest that BAL oil red O positive macrophages are frequently observed in trauma patients irrespective of the presence of fat embolism syndrome. Conceivably, a high number of oil red O positive macrophages could reflect clinically silent fat embolization.
Activated and memory alveolar T-lymphocytes in idiopathic eosinophilic pneumonia
Authors: Albera C , Ghio P , Solidoro P , Mabritto I , Marchetti L , Pozzi E
Published: August 2003

To investigate the possible involvement of T-lymphocytes in the immunopathogenesis of idiopathic eosinophilic pneumonia (IEP), we have evaluated the phenotypic characteristics both of peripheral blood and alveolar lymphocytes in six patients with symptomatic IEP, and in 24 healthy nonsmokers as controls, by employing bronchoalveolar lavage (BAL), monoclonal antibodies, and flow-cytometry. In IEP, total and differential cell counts showed a mild alveolitis with an increase of eosinophil percentage and number; the alveolar lymphocyte count was also increased. In BAL, the total number both of CD4+ and CD8+ lymphocytes was significantly raised; CD4+ cells expressed early (CD25) activation antigens. The analysis of CD45R0, CD45RA and CD62L coexpression in IEP patients, when compared to healthy controls, revealed an accumulation of alveolar CD4+ cells showing phenotypic repertoire usually expressed by memory T-cells (CD45R0+, CD45RA-, CD62L-). CD8+ alveolar lymphocytes did not show any significant increase of activation antigen coexpression. Circulating lymphocytes were not significantly increased and showed only a significantly higher CD25 expression. These data suggest that a pivotal role is played by activated and memory CD4+ alveolar lymphocytes in IEP patients.
Increased oxidation of extracellular glutathione by bronchoalveolar inflammatory cells in diffuse fibrosing alveolitis
Authors: Behr J , Degenkolb B , Maier K , Braun B , Beinert T , Krombach F , Vogelmeier C , Fruhmann G
Published: August 2003

An unbalanced oxidative stress is thought to be an important element in the pathogenesis of diffuse fibrosing alveolitis (DFA). The purpose of our study was to investigate the role of reactive oxygen metabolites (ROMs) released from cultured bronchoalveolar inflammatory cells (BA-cells) on glutathione oxidation. We studied bronchoalveolar lavage samples from 10 healthy controls and from 20 patients with diffuse fibrosing alveolitis (all were nonsmokers). BA-cells obtained by bronchoalveolar lavage (BAL) were incubated with 50 microM of reduced glutathione (GSH). Oxidation of GSH to glutathione disulphide (GSSG) by BA-cell derived oxidants was detected as a decline of GSH in the supernatants. Total glutathione (GSHtot = GSH + 2 GSSG) and GSSG in the epithelial lining fluid (ELF), and methionine sulphoxide (Met(O)) content of BAL proteins were determined. In diffuse fibrosing alveolitis the oxidative activity of BA-cells was enhanced, GSHtot and GSH were decreased, whereas the GSSG:GSH ratio was increased. The oxidative activity of BA-cells correlated positively with the GSSG:GSH ratio, but not with the methionine sulphoxide content. The methionine sulphoxide content was elevated in diffuse fibrosing alveolitis and inversely correlated with GSHtot. The methionine sulphoxide content also correlated positively with the percentage of BAL neutrophils. We conclude that BA-cell-derived reactive oxygen species are capable of oxidizing extracellular GSH in vitro. The positive correlation between the BA-cell oxidative activity in vitro and GSSG:GSH ratio in ELF suggests that a similar oxidative effect on extracellular GSH may also occur in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
A specific neutrophil elastase inhibitor (ONO-5046.Na) attenuates LPS-induced acute lung inflammation in the hamster
Authors: Yasui S , Nagai A , Aoshiba K , Ozawa Y , Kakuta Y , Konno K
Published: August 2003

We have examined the effect of ONO-5046.Na, a synthetic specific inhibitor of neutrophil elastase, on lipopolysaccharide (LPS)-induced acute lung inflammation. Syrian golden hamsters were injected intraperitoneally with either 300 mg.kg-1 of ONO-5046.Na or saline, 30 min before and 1 h after intratracheal administration of 0.1 mg.kg-1 LPS. Animals were sacrificed 2 and 24 h later and the wet-to-dry lung weight ratio (W/D) was determined. Bronchoalveolar lavage (BAL) was performed, and tissue sections were examined histologically. The effect of ONO-5046.Na on migration of isolated neutrophils was determined. W/D was not significantly different at 2 h, but was increased at 24 h in the LPS-treated animals. This increase was attenuated in the LPS-treated animals injected with ONO-5046.Na. Analysis of BAL fluid revealed that both at 2 and 24 h after LPS administration the total cell number and neutrophil number, albumin concentration, and elastase-like activity were significantly lower in the LPS-treated animals injected with ONO-5046.Na than in those given LPS alone. Histological examination of the lungs of the animals treated with LPS alone showed intra-alveolar haemorrhages and inflammatory cell infiltration 24 h after LPS administration, whereas the lungs of the LPS-treated ONO-5046.Na injected animals were only sparsely infiltrated by inflammatory cells, as indicated by the inflammation score.(ABSTRACT TRUNCATED AT 250 WORDS)
Interstitial pneumonitis-like lesions in guinea-pigs following repeated exposure to toluene diisocyanate
Authors: Yamada K , Amitani R , Niimi A , Kuze F
Published: August 2003

The inhalation of isocyanates, such as toluene diisocyanate (TDI), diphenylmethane diisocyanate (MDI), and hexamethylene diisocyanate (HDI) can induce hypersensitivity pneumonitis (HP) as well as bronchial asthma in humans, but the precise pathological features and their pathogenetic mechanisms have not been elucidated. To provide insight into the pathological features of isocyanate-induced hypersensitivity pneumonitis in humans, we repeatedly exposed guinea-pigs to TDI following previous sensitization to TDI and examined the inflammatory response in the pulmonary lesions. Following sensitization with 10% TDI ethyl acetate solution for seven consecutive days, guinea-pigs were exposed to 5% TDI ethyl acetate solution once a week for 4 weeks. As a control, guinea-pigs were exposed to ethyl acetate alone in the same manner. Furthermore, other guinea-pigs received a single exposure to 5 or 20% TDI ethyl acetate solution. The TDI solutions or ethyl acetate were applied to the bilateral nasal mucosa of guinea-pigs for 30 s-day-1. Histological examination of lung specimens of guinea-pigs repeatedly exposed to TDI after previous sensitization by TDI inhalation revealed interstitial pneumonitis-like lesions in which mononuclear cells and eosinophils were mainly involved. Lungs of control and nonsensitized guinea-pigs showed insignificant histological changes. We demonstrated that interstitial pneumonitis-like lesions, indistinguishable from isocyanate-induced hypersensitivity pneumonitis in humans, can be caused by repeated but not single exposure to TDI in guinea-pigs.
Forced oscillation technique (FOT): a new tool for epidemiology of occupational lung diseases?
Authors: Pham QT , Bourgkard E , Chau N , Willim G , Megherbi SE , Teculescu D , Bohadana A , Bertrand JP
Published: August 2003

The aim of this study was to evaluate the usefulness of the forced oscillation technique (FOT) in the assessment of occupation-related airway changes. The forced oscillation technique and conventional lung function tests were applied in 80 underground coalface workers, aged 35-48 yrs, with chest roentgenogram films classified 0/1 or 1/0 according to the International Labour Office (ILO) classification (G group), and two control groups matched for age and smoking habits. The first control group, was made up of face-workers having normal chest radiographs, whilst the second comprised underground non-face-workers with normal chest radiographs. Spirometric, plethysmographic and transfer factor of the lungs for carbon monoxide single-breath (TL,CO,sb) indices revealed no significant differences between the three groups. As regards the forced oscillation technique, a higher value of resistance/frequency slope (Pa.L-1.s2) was found in the G group compared with the control groups; 2.11 vs 1.06 in the face-workers, and 1.58 in the underground workers. In all three groups, the forced oscillation technique indices (mean resistance (R), resistance at zero frequency (RO), resistance/frequency slope (S), and resonant frequency (fo)) were found to be higher in subjects having a decreased forced expiratory volume in one second (FEV1) (< or = 90% predicted) or a mildly obstructive pattern of ventilatory function, even though this did not reach statistical significance in each of the groups. These findings together with the feasibility and acceptability of the forced oscillation technique would suggest that it may be a suitable tool for epidemiological studies of occupational respiratory diseases.
Exercise-induced airway narrowing in army recruits with a history of childhood asthma
Authors: Sinclair DG , Sims MM , Hoad NA , Winfield CR
Published: August 2003

The aim of this study was to determine whether the addition of cold, dry, inspired air to maximum heart rate (MHR) exercise increased the number of subjects demonstrating abnormal airway narrowing, when applied to symptom-free army recruits with a history of asthma in childhood. One hundred recruits with a history of asthma in childhood underwent two exercise challenges to maximum heart rate, breathing either room air or cold dry air in randomized order. The percentage fall index (%FI) was calculated for each challenge, a positive result being > or = 15%. A total of 29 subjects had a positive % fall index, 12 subjects were positive to both challenges, 7 to the room air alone and 10 to the cold air challenge alone. In these subjects (n = 29), the mean (SD) % fall index to the cold air challenge was 22.7 (11.0)% compared with 16.3 (9.5)% for the room air challenge. We conclude that when employed as a screening test for abnormal airway narrowing, the addition of cold, dry, inspired air during exercise does not increase the number of subjects with a positive response, but the magnitude of the response is increased.
Preventive therapy for asthma in children; a 9-year experience in eastern Finland
Authors: Korppi M , Kuikka L , Remes K
Published: August 2003

The long-term treatment modalities of bronchial asthma were studied in children from a defined Finnish population from 1985 to 1993, with special reference to changes during the study period. The data on maintenance drugs in children with asthma from five years (1985, 1987, 1989, 1991 and 1993) were retrospectively retrieved from the computerized registers. The reliability of the data for the diagnosis and basic treatment of asthma was checked by one of the authors, who compared the data with the patient cards from the hospital. The number of children with doctor-diagnosed asthma increased continuously during the surveillance period. The proportion of children receiving preventive medication increased concomitantly; this increase was most pronounced between 1987 and 1989. The most common preventive drug was sodium cromoglycate; its use increased from 14% in 1985 to 58% in 1993. The use of inhaled steroids remained stable at 17-19% in all surveillance years. Our treatment policy is in accordance with the international consensus statement published in 1989; however, the change towards preventive medication occurred before its publication.
Modulation of the bronchial inflammation in sensitized guinea-pigs by FK506, nedocromil sodium and dexamethasone
Authors: Lapa Silva e , Ruffie C , Vargaftig BB , Pretolani M
Published: August 2003

Guinea-pigs sensitized by a subcutaneous injection of ovalbumin in Al(OH)3 and boosted 2 weeks later exhibit marked bronchial hyperresponsiveness to various agonists and intense bronchial wall infiltration by CD4+ T-lymphocytes and eosinophils. We have compared the effect of FK506, a novel immunosuppressive agent, on the mucosal infiltration by T-cells and eosinophils with the well established drugs, nedocromil sodium and dexamethasone. Sensitized Hartley guinea-pigs were treated subcutaneously for 5 days with FK506 (100 micrograms.kg-1 daily), nedocromil sodium (30 micrograms.kg-1 daily), or dexamethasone (200 micrograms.kg-1 daily). On the day of the experiment, i.e. one week after the booster injection of antigen, the animals were killed, the lungs dissected, frozen and cryostat sections stained by immunohistochemical methods using monoclonal antibodies specific for total T-lymphocytes, CD4+ and CD8+ T-cells. Cyanide-resistant eosinophil peroxidase activity was used to stain the eosinophils. Sections were coded and positive cells enumerated in the lamina propria and adventitia of the bronchi. Sensitized and antigen-stimulated vehicle-treated guinea-pigs showed marked infiltration of the bronchial wall by CD4+ T-lymphocytes and eosinophils compared with sensitized, non-antigen stimulated animals. As compared to vehicle, FK506 or dexamethasone abolished the T-cell/eosinophil invasion in the bronchial wall, whereas nedocromil sodium was ineffective in protecting the lungs from T-lymphocyte or eosinophil infiltration. We conclude that both FK506 and dexamethasone are effective in curtailing bronchial inflammation in allergic guinea-pigs, whereas nedocromil sodium did not resolve the inflammation associated with T-lymphocytes or eosinophils.
Influence of endothelial nitric oxide on neurogenic contraction of human pulmonary arteries
Authors: Martinez C , Cases E , Vila JM , Aldasoro M , Medina P , Marco V , Lluch S
Published: August 2003

The present study was designed to investigate the contribution of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human pulmonary arteries to electrical field stimulation (EFS) and noradrenaline. Isometric tension was measured in artery rings obtained from portions of human lung after thoracic surgery for removal of lung carcinoma (18 patients). Electrical field stimulation (EFS) induced frequency-dependent contractions of isolated human pulmonary arteries which were abolished by tetrodotoxin, guanethidine and prazosin (all at 10(-6) M). The increases in tension were of greater magnitude in arteries denuded of endothelium. NG-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) potentiated the contractile response to EFS in artery rings with endothelium but not in endothelium-denuded arteries. The potentiation induced by L-NAME was completely reversed by L-arginine (10(-4) M) but not by D-arginine (10(-4) M). Indomethacin (3 x 10(-6) M) had no significant effect on the contractile response to EFS. Contractile responses to noradrenaline were similar in arteries with and without endothelium. Our results suggest that electrical field stimulation releases endothelium-derived nitric oxide, which inhibits the contractile responses of human pulmonary arteries. Although adrenergic nerves seem to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be noradrenaline.
Chronic mucus hypersecretion in COPD and death from pulmonary infection
Authors: Prescott E , Lange P , Vestbo J
Published: August 2003

The association of chronic mucus hypersecretion and mortality is a matter of debate. We wished to determine whether the relationship between chronic mucus hypersecretion and chronic obstructive pulmonary disease (COPD)-related mortality could be explained by proneness to pulmonary infection. We followed 14,223 subjects of both sexes for 10-12 yrs. Cases where COPD was an underlying or contributory cause of death (n = 214) were included, and hospital records were obtained when possible (n = 101). From the presence of increased mucus, purulent mucus, fever, leucocytosis and infiltration on chest radiography, death was classified as either due to pulmonary infection (n = 38), other causes (n = 51), or unclassifiable (n = 12). Of subjects reporting chronic mucus hypersecretion at the initial examination, pulmonary infection was implicated in 54% of deaths, whereas this only occurred in 28% of subjects without chronic mucus hypersecretion. Controlling for covariates, in particular smoking habits, a Cox analysis showed a strong inverse relationship between ventilatory function and COPD-related mortality. Chronic mucus hypersecretion was found to be a significant predictor of COPD-related death with pulmonary infection implicated (relative risk (RR) 3.5) but not of death without pulmonary infection (RR 0.9). We consider that subjects with COPD and chronic mucus hypersecretion are more likely to die from pulmonary infections than subjects without chronic mucus hypersecretion. This may explain the excess mortality in subjects with COPD and chronic mucus hypersecretion found in previous studies.
Functional outcome of patients with chronic obstructive pulmonary disease and exercise hypercapnia
Authors: Simard AA , Maltais F , LeBlanc P
Published: August 2003

Chronic hypercapnia is associated with a poor prognosis in chronic obstructive pulmonary disease (COPD). Some patients are normocapnic at rest but retain CO2 during exercise. The significance of this abnormality on the course of the disease is unknown. Sixteen stable COPD patients (13 males and 3 females, aged 60 +/- 5 yrs, mean +/- SD) who had previously undergone pulmonary function tests and progressive exercise testing with arterial blood sampling at rest and maximal capacity, entered the study. At first evaluation (E1), subjects were normocapnic at rest (arterial carbon dioxide tension (Pa,CO2): 4.9-5.7 kPa, (37-43 mmHg)) and all presented exercise-induced hypercapnia (end-exercise Pa,CO2 > 5.7 kPa (43 mmHg) with a minimal 0.5 kPa (4 mmHg) increase from resting value). The subjects were re-evaluated 24-54 months later (34 +/- 8 months) (second evaluation (E2)). At E2, forced expiratory volume in one second (FEV1) had decreased from 42 +/- 13 to 38 +/- 15% of predicted values, and mean resting Pa,CO2 had increased from 5.2 +/- 0.3 to 5.7 + 0.4 kPa. Maximal exercise capacity (Wmax) decreased between E1 and E2 from 76 +/- 30 to 56 +/- 22 W. Even if Wmax was lower at E2, end-exercise, Pa,CO2 was higher than at E1 (6.6 +/- 0.8 vs 6.4 +/- 0.5 kPa). At E2, eight subjects presented resting hypercapnia (group H), whilst the others remained normocapnic (Group N). Group H subjects had higher Pa,CO2, at Wmax than Group N and lower Wmax than Group N at E2.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolic and ventilatory response pattern to arm elevation in patients with COPD and healthy age-matched subjects
Authors: Baarends EM , Schols AM , Slebos DJ , Mostert R , Janssen PP , Wouters EF
Published: August 2003

Many patients with chronic obstructive pulmonary disease (COPD) experience problems in those activities of daily living which involve so-called unsupported arm elevations (AE). In this study, possible differences in the metabolic and ventilatory response pattern to three types of arm elevation were compared between 13 COPD patients (forced expiratory volume in one second (FEV1) (mean (SD)) 38 (13)% of predicted) and 13 age-matched healthy subjects. Each subject consecutively performed three types of arm elevation for 2 min, with 3 min rest periods in between. Breath-by-breath metabolic and ventilatory parameters and heart rate (HR) were registered during a 3 min baseline period and throughout the measurement period. Adjusted for significantly greater baseline test results in COPD patients, it was found that AE (arm elevation including recovery) tended to be more demanding with respect to metabolic and ventilatory response for patients with COPD than for the age-matched healthy subjects. Arm elevation resulted in an increase in oxygen consumption (V'O2) (COPD 12%; healthy 6%), carbon dioxide elimination V'CO2 (COPD 15%; healthy 10%), minute ventilation V'E (COPD 13%; healthy 7%) and heart rate (COPD 2%; healthy 5%). A pronounced difference was found in the pattern of metabolic and ventilatory response to arm elevation, i.e. there was an earlier but sluggish V'O2 onset in COPD patients, whereas the healthy subjects demonstrated a sudden peak approximately 30 s after arm elevations. Mutual comparison of the three different types of arm elevation demonstrated a comparable response pattern. Knowledge of the specific response to arm elevations in COPD patients seems essential for interpretation of arm elevation tests in upper extremity rehabilitation programmes.
Fibrinolytic and inflammatory processes in pleural effusions
Authors: Philip-Joet F , Alessi MC , Philip-Joet C , Aillaud M , Barriere  , Arnaud A , Juhan-Vague I
Published: August 2003

This study was designed to evaluate major fibrinolytic parameters in relation to parameters of inflammation associated with different kinds of pleural effusion. Sixty patients with pleural effusion were studied. The underlying aetiology was empyema in 10 cases, tuberculosis in 9, cancer in 31, cardiac failure in 7, and undetermined in 3. Plasminogen, plasminogen activator inhibitor 1 (PAI-1) and 2 (PAI-2), tissue type plasminogen activator (t-PA), urokinase (u-PA) and D-dimers (D-D) were quantified in plasma samples and pleural effusion specimens. These data were then correlated with inflammatory or infectious parameters, i.e. fibrinogen, von Willebrand factor (vWF), erythrocyte sedimentation rate (ESR), protein concentration, and white blood cell count. D-D levels were higher in pleural fluid than in plasma. D-D levels were not correlated with either plasminogen activator or plasminogen activator inhibitor levels, suggesting the presence of other fibrinolytic pathways. PAI levels (PAI activity, PAI-1 antigenicity, PAI-2 antigenicity) and vWF levels were significantly higher in patients with tuberculosis and empyema than in patients with cancer or cardiac failure. Regression analysis between inflammatory and fibrinolytic parameters showed that pleural PAI levels were significantly correlated with pleural neutrophil count, vWF levels, and plasma fibrinogen levels. D-D levels were correlated with blood ESR. No significant difference in pleural t-PA, u-PA and D-D levels was observed between aetiologies. The highest pleural t-PA and u-PA values were noted in patients with cancer, especially lymphoma. Plasma t-PA levels were higher inpatients with pleural effusion secondary to congestive heart failure, but this difference did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of oxidant air pollutants on the respiratory system: insights from experimental animal research
Authors: Chitano P , Hosselet JJ , Mapp CE , Fabbri LM
Published: August 2003

In the present paper, we have reviewed experimental animal studies on the effects of the two most important oxidant airborne pollutants, nitrogen dioxide and ozone, on the respiratory system. The toxic effects depend on concentration and length of exposure, and are generally similar for both oxidants, with ozone operative at lower concentrations. High doses of both oxidants cause death due to lung oedema. Exposure to sublethal levels causes functional alterations such as airflow limitation and airway hyperresponsiveness to bronchoconstrictor stimuli. These effects, which are generally reversible, are associated with epithelial injury, oedema and airway and parenchymal infiltration by inflammatory cells. Loss of cilia of airway epithelium and necrosis of type I alveolar epithelial cells are the most prominent consequences at the epithelial level. Inflammation is characterized by early neutrophilic infiltration, followed by an increased number of mononuclear cells, predominantly alveolar macrophages. After long-term exposure, whilst nitrogen dioxide causes predominantly emphysema, ozone produces mainly pulmonary fibrosis. Biochemical effects include lipid peroxidation, increased antioxidant metabolism, and alteration of enzyme activity. Nitrogen dioxide and ozone may also alter the immunological response and reduce the defence against infections, increasing the susceptibility of exposed animals to infections.
Central sleep apnoea, pathogenesis and treatment: an overview and perspective
Authors: De Backer WA
Published: August 2003

The prevalence of reported sleep disturbances in a general population is high. Many of the complaints are the result of sleep-related breathing disorders, due mainly to the occurrence of obstructive and central apnoeas. Obstructive sleep apnoea is a fully described and well-recognized entity. Central sleep apnoea (CSA) however, has been poorly studied. There is accumulating evidence that central sleep apnoea should be considered as the end of a spectrum. Instability in the breathing pattern is the main underlying mechanism and is due to the interaction of many factors. Breathing during sleep is dependent on metabolic control and the activity of the respiratory muscles. Decreased chemical drive and/or failing respiratory muscle function are associated with CSA and usually also with ongoing hypoventilation during wakefulness, characterized by chronic daytime hypercapnia. Central respiratory drive can also be inhibited by upper airway reflexes. Mostly, however, CSA occurs as the hallmark of unstable breathing during sleep brought about by an overall increase in loop gain (especially in light sleep stages) and the unmasking of a CO2 threshold. Arousal following central apnoeas acts as an amplification of the instability. Micro electroencephographic (EEG) arousals are often observed as a consequence of CSA. They are responsible for sleep fragmentation and hypersomnolence during the day. The daytime hypersomnolence and complaints of awakenings during sleep in patients with CSA can be striking. CSA can occur in specific pathologies, such as chronic heart failure and (post-traumatic) brain lesions, that are associated with irregular breathing. Treatment strategies are remarkably few in number. Use of nasal ventilation and the inhalation of CO2 are mainly of theoretical interest, since patients do not often tolerate these more invasive therapies. Drug treatment, especially with acetazolamide, is easier to perform. Stimulation of upper airway reflexes, by less invasive methods, seems to be promising for the near future.
Anti-tuberculosis medication and the liver: dangers and recommendations in management
Authors: Thompson NP , Caplin ME , Hamilton MI , Gillespie SH , Clarke SW , Burroughs AK , McIntyre N
Published: August 2003

In the light of three deaths due to liver failure secondary to anti-tuberculosis therapy at the Royal Free Hospital, we have reviewed the current literature, and asked--How common is liver dysfunction with anti-tuberculosis medications and how might it be prevented? Anti-tuberculosis chemotherapy is associated with abnormalities in liver function tests in 10-25% of patients. Clinical hepatitis develops in about 3%, though estimates vary, and in these patients there is likely to be significant morbidity and mortality. On the basis of reported cases of tuberculosis, 160 patients in England and Wales can be expected to develop drug-induced hepatitis due to anti-tuberculosis therapy each year. There are published guidelines from the British and American Thoracic Societies regarding the choice of drug therapy for tuberculosis. Current recommendations with regard to monitoring liver function, and what to do when these tests become abnormal, vary considerably. We suggest a protocol for using liver function tests to monitor for liver damage, and give recommendations on what action to take when these become abnormal.
Molecular and biological factors in the prognosis of non-small cell lung cancer
Authors: Kanters SD , Lammers JW , Voest EE
Published: August 2003

For patients with non-small cell lung cancer the tumour/node/metastasis (TNM) staging system and other conventional prognostic factors fail to predict the outcome of treatment and survival accurately. New prognostic factors are urgently needed to improve understanding of the biological behaviour of the different subtypes of non-small cell lung cancer and to recognize patients with a good or poor prognosis. This review will focus on molecular and biological factors published in the English language literature between 1988 and 1994. To be included in this survey, the predictive value of a specific prognostic factor had to be confirmed by multivariate analysis in at least two different studies. Blood group antigen expression, ras oncogenes, microvessel density, and factors reflecting the proliferative state of the tumour may be important determinants of outcome of treatment. The search for new determinants of prognosis has provided insight in the complex tumour biology of non-small cell lung cancer and indicated possible targets for tumour therapy. Several promising prognostic factors have now been recognized. To validate these factors, prospective studies of a large patient population are needed. This ultimately serves the recognition of subsets of patients who may benefit from adjuvant therapy.
Occupational asthma due to ceftazidime
Authors: Stenton SC , Dennis JH , Hendrick DJ
Published: August 2003

A worker employed in the manufacture of the new third generation cephalosporin antibiotic, ceftazidime, developed asthmatic symptoms, and a series of inhalation challenge tests was undertaken to investigate the problem. The inhalation of increasing daily doses of ceftazidime up to 3.2 mg, using a double-blind challenge protocol gave rise to symptoms, late asthmatic reactions, and increases in airway responsiveness to methacholine. A repeat challenge with the 3.2 mg dose additionally gave rise to a clear immediate reaction. Ceftazidime was, thus, shown to be capable of inducing occupational asthma.
Normal pregnancy in primary alveolar hypoventilation treated with nocturnal nasal intermittent positive pressure ventilation
Authors: Pieters T , Amy JJ , Burrini D , Aubert G , Rodenstein DO , Collard P
Published: August 2003

Nocturnal nasal intermittent positive pressure ventilation (NIPPV) is increasingly used to treat chronic respiratory failure in a wide variety of conditions (myopathies, Ondine's curse, kyphoscoliosis, etc.) and allows a normal everyday life. Some of these diseases affect women of childbearing age. We report on a young woman suffering from primary alveolar hypoventilation, who presented with limitation of daytime activities, severe oxygen desaturation during sleep, polycythaemia and pulmonary hypertension. These abnormalities completely reversed after a few months of NIPPV applied through a nasal mask. Whilst under ventilatory assistance during sleep, she had an uneventful pregnancy and delivery of a normal baby. We suggest that in selected patients requiring NIPPV, pregnancy can be contemplated with a reasonable level of safety both for the mother and the child, provided that adequate mechanical ventilatory assistance during sleep is maintained throughout pregnancy.
Mycobacterium avium-intracellulare pleuritis with massive pleural effusion
Authors: Okada Y , Ichinose Y , Yamaguchi K , Kanazawa M , Yamasawa F , Kawashiro T
Published: August 2003

Atypical mycobacterial infection is seldom accompanied by pleural involvement. We report a very rare case of Mycobacterium avium-intracellulare pleuritis with massive pleural effusion. The patient was a non-immunocompromised 35-year-old Japanese male with insidious onset of fever, chest pain and anorexia. The pleural effusion gradually resolved with empirical antimycobacterial treatment, leaving considerable pleural adhesion and thickening.
Malignant fibrous histiocytoma presenting as an endobronchial polyp of the carina
Authors: Shijubo N , Sugaya F , Imada A , Kudoh K , Suzuki A , Nakata H , Satoh M , Abe S
Published: August 2003

A 64 year old man was admitted to hospital due to dyspnoea and stridor. A peduncular polyp of the carina was found at bronchoscopy. Histological examination of the tumour after resection with endoscopic electronsurgery revealed malignant fibrous histiocytoma (MFH) of myxoid type. With endoscopic neodymiumyttrium aluminium garnet (Nd-YAG) laser surgery, residual tumour was eliminated. To our knowledge this is the first case with malignant fibrous histiocytoma appearing as a polyp of the carina.
Regulation of apoptosis in theXenopusembryo by Bix3
Authors: Trindade Margarida , Messenger Nigel , Papin Catherine , Grimmer Donna , Fairclough Lynne , Tada Masazumi , Smith James C.
Published: August 2003

Members of the Bix family of homeobox-containing genes are expressed in the vegetal hemisphere of the Xenopus embryo at the early gastrula stage. Misexpression of at least some of the family members causes activation of mesoderm- and endoderm-specific genes and it is known that some of the proteins, including Bix2 and Bix3, interact with Smad proteins via a motif that is also present in the related protein Mixer. In this paper we study the function of Bix3. Misexpression of Bix3, similar to misexpression of other members of the Bixfamily, causes the activation of a range of mesendodermal genes, but the spectrum of genes induced by Bix3 differs from that induced by Bix1. More significantly, we find that overexpression of Bix3 also causes apoptosis, as does depletion of Bix3 by use of antisense morpholino oligonucleotides. The ability of Bix3 to causes apoptosis is not associated with its ability to activate transcription and nor with its possession of a Smad interaction motif. Rather, Bix3 lacks a C-terminal motif,which, in Bix1, acts in cis to inhibit apoptosis. Mutation of this sequence in Bix1 causes the protein to acquire apoptosis-inducing activity.
Secondary chondrocyte-derived Ihh stimulates proliferation of periosteal cells during chick development
Authors: Buxton Paul G. , Hall Brian , Archer Charles W. , Francis-West Philippa
Published: August 2003

The development of the skull is characterised by its dependence upon epigenetic influences. One of the most important of these is secondary chondrogenesis, which occurs following ossification within certain membrane bone periostea, as a result of biomechanical articulation. We have studied the genesis, character and function of the secondary chondrocytes of the quadratojugal of the chick between embryonic days 11 and 14. Analysis of gene expression revealed that secondary chondrocytes formed coincident with Sox9 upregulation from a precursor population expressing Cbfa1/Runx2: a reversal of the normal sequence. Such secondary chondrocytes rapidly acquired a phenotype that is a compound of prehypertrophic and hypertrophic chondrocytes, exited from the cell cycle and upregulated Ihh. Pulse and pulse/chase experiments with BrdU confirmed the germinal region as the highly proliferative source of the secondary chondrocytes, which formed by division of chondrocyte-committed precursors. By blocking Hh signalling in explant cultures we show that the enhanced proliferation of the germinal region surrounding the secondary chondrocytes derives from this Ihh source. Additionally, in vitro studies on membrane bone periosteal cells (non-germinal region) demonstrated that these cells can also respond to Ihh, and do so both by enhanced proliferation and precocious osteogenesis. Despite the pro-osteogenic effects of Ihh on periosteal cell differentiation, mechanical articulation of the quadratojugal/quadrate joint in explant culture revealed a negative role for articulation in the regulation of osteocalcin by germinal region descendants. Thus, the mechanical stimulus that is the spur to secondary chondrocyte formation appears able to override the osteogenic influence of Ihh on the periosteum, but does not interfere with the cell cycle-promoting component of Hh signalling.
The lipid phosphatase LPP3 regulates extra-embryonic vasculogenesis and axis patterning
Authors: Escalante-Alcalde Diana , Hernandez Lidia , Le Stunff Hervé , Maeda Ryu , Lee Hyun-Shik , Cheng Gang , Sciorra Vicki A. , Daar Ira , Spiegel Sarah , Morris Andrew J. , Stewart Colin L.
Published: August 2003

Bioactive phospholipids, which include sphingosine-1-phosphate,lysophosphatidic acid, ceramide and their derivatives regulate a wide variety of cellular functions in culture such as proliferation, apoptosis and differentiation. The availability of these lipids and their products is regulated by the lipid phosphate phosphatases (LPPs). Here we show that mouse embryos deficient for LPP3 fail to form a chorio-allantoic placenta and yolk sac vasculature. A subset of embryos also show a shortening of the anterior-posterior axis and frequent duplication of axial structures that are strikingly similar to the phenotypes associated with axin deficiency,a critical regulator of Wnt signaling. Loss of LPP3 results in a marked increase in β-catenin-mediated TCF transcription, whereas elevated levels of LPP3 inhibit β-catenin-mediated TCF transcription. LPP3 also inhibits axis duplication and leads to mild ventralization in Xenopusembryo development. Although LPP3 null fibroblasts show altered levels of bioactive phospholipids, consistent with loss of LPP3 phosphatase activity, mutant forms of LPP3, specifically lacking phosphatase activity, were able to inhibit β-catenin-mediated TCF transcription and also suppress axis duplication, although not as effectively as intact LPP3. These results reveal that LPP3 is essential to formation of the chorio-allantoic placenta and extra-embryonic vasculature. LPP3 also mediates gastrulation and axis formation, probably by influencing the canonical Wnt signaling pathway. The exact biochemical roles of LPP3 phosphatase activity and its undefined effect on β-catenin-mediated TCF transcription remain to be determined.
Isolation of pigment cell specific genes in the sea urchin embryo by differential macroarray screening
Authors: Calestani Cristina , Rast Jonathan P. , Davidson Eric H.
Published: August 2003

New secondary mesenchyme specific genes, expressed exclusively in pigment cells, were isolated from sea urchin embryos using a differential screening of a macroarray cDNA library. The comparison was performed between mRNA populations of embryos having an expansion of the endo-mesodermal territory and embryos blocked in secondary mesenchyme specification. To be able to isolate transcripts with a prevalence down to five copies per cell, a subtractive hybridization procedure was employed. About 400 putative positive clones were identified and sequenced from the 5′ end. Gene expression analysis was carried out on a subset of 66 clones with real time quantitative PCR and 40 clones were positive. This group of clones contained sequences highly similar to: the transcription factor glial cells missing(gcm); the polyketide synthase gene cluster (pks-gc); three different members of the flavin-containing monooxygenase gene family(fmo); and a sulfotransferase gene (sult). Using whole mount in situ hybridization, it was shown that these genes are specifically expressed in pigment cells. A functional analysis of the S. purpuratus pks and of one S. purpuratus fmo was carried out using antisense technology and it was shown that their expression is necessary for the biosynthesis of the sea urchin pigment echinochrome. The results suggest that S. purpuratus pks, fmo and sult could belong to a differentiation gene battery of pigment cells.
Metaphase I arrest of starfish oocytes induced via the MAP kinase pathway is released by an increase of intracellular pH
Authors: Harada Kaori , Oita Eiko , Chiba Kazuyoshi
Published: August 2003

Reinitiation of meiosis in oocytes usually occurs as a two-step process during which release from the prophase block is followed by an arrest in metaphase of the first or second meiotic division [metaphase I (MI) or metaphase II (MII)]. The mechanism of MI arrest in meiosis is poorly understood, although it is a widely observed phenomenon in invertebrates. The blockage of fully grown starfish oocytes in prophase of meiosis I is released by the hormone 1-methyladenine. It has been believed that meiosis of starfish oocytes proceeds completely without MI or MII arrest, even when fertilization does not occur. Here we show that MI arrest of starfish oocytes occurs in the ovary after germinal vesicle breakdown. This arrest is maintained both by the Mos/MEK/MAP kinase pathway and the blockage of an increase of intracellular pH in the ovary before spawning. Immediately after spawning into seawater,activation of Na+/H+ antiporters via a heterotrimeric G protein coupling to a 1-methyladenine receptor in the oocyte leads to an intracellular pH increase that can overcome the MI arrest even in the presence of active MAP kinase.
Reelin signaling directly affects radial glia morphology and biochemical maturation
Authors: Hartfuss Eva , Förster Eckart , Bock Hans H. , Hack Michael A. , Leprince Pierre , Luque Juan M. , Herz Joachim , Frotscher Michael , Götz Magdalena
Published: August 2003

Radial glial cells are characterized, besides their astroglial properties,by long radial processes extending from the ventricular zone to the pial surface, a crucial feature for the radial migration of neurons. The molecular signals that regulate this characteristic morphology, however, are largely unknown. We show an important role of the secreted molecule reelin for the establishment of radial glia processes. We describe a significant reduction in ventricular zone cells with long radial processes in the absence of reelin in the cortex of reeler mutant mice. These defects were correlated to a decrease in the content of brain lipid-binding protein (Blbp) and were detected exclusively in the cerebral cortex, but not in the basal ganglia of reeler mice. Conversely, reelin addition in vitro increased the Blbp content and process extension of radial glia from the cortex, but not the basal ganglia. Isolation of radial glia by fluorescent-activated cell sorting showed that these effects are due to direct signaling of reelin to radial glial cells. We could further demonstrate that this signaling requires Dab1, as the increase in Blbp upon reelin addition failed to occur in Dab1-/-mice. Taken together, these results unravel a novel role of reelin signaling to radial glial cells that is crucial for the regulation of their Blbp content and characteristic morphology in a region-specific manner.