bluuebunny/crossref_metadata_2025 huggingface dataset:
BOULDERS, NATIVE PRAIRIE AND A THEISTIC STEWARDSHIP ETHIC
Authors: Reichenbach Bruce
Published: June 2003

The recent fad of removing glacial boulders from native Midwest prairie to create walls for urban wildflower gardens provides the context for thinking about how a theistic stewardship ethic addresses the environment. The three commands of Genesis 1 and 2 provide the basis for a theistic stewardship ethic, where God as the Creator/Landowner establishes humans as stewards to administer his kingdom. Contrary to the oft-repeated view that the injunction to rule over justifies a mere instrumental use and hence abuse of the environment, the command gives value to the biotic environment because the created has interests and thereby moral standing. Consequently, the environment must be considered in the for-whom of moral calculation. However, a theistic environmental ethic adds that the value of nature is neither merely intrinsic nor instrumental, but derives from the value accorded it by its Creator, who in seeing it function declares it good. The command to care for allows for sustainable conservation and human use rather than mere preservation. And the command to fill connects with the need to preserve and foster genetic and ecological diversity. Throughout we apply these commands to the case study about boulders and native prairie.
ENVIRONMENTAL UNDERSTANDING: SACRED COWS NEED CULLING
Authors:   Berry
Published: June 2003

Attitudes towards the natural world are complicated by all sorts of preconceptions and out-dated ideas. Some of these arise from different interpretations of the same data, but others are hangovers from past debates in science, philosophy or religion. The result is a herd of 'sacred cows' which need drastic culling. I suggest that Francis Bacon's insistence that we should read both Books of God—of words (the Bible) and of works (scientific understanding)—is a key part of this process; it could provide a positive way of testing scientific and theological interpretations, and hopefully undergird progress towards a sensible basis for a robust environmental ethic.
HGF receptor up-regulation contributes to the angiogenic phenotype of human endothelial cells and promotes angiogenesis in vitro
Authors: Ding Shunli , Merkulova-Rainon Tatyana , Han Zhong Chao , Tobelem Gérard
Published: June 2003

Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic growth factor and a powerful stimulator of angiogenesis, which acts on cells by binding to the c-met receptor. The exact role of the endogenous HGF/c-met system in one or more steps of the angiogenic process is not completely understood. To contribute to this question we used immunocytochemical analysis, Western blotting, and reverse transcription–polymerase chain reaction to study the expression of c-met in endothelial cells cultured in different growth conditions. We found that c-met is not colocalized with vascular endothelial (VE)–cadherin in cell-cell junctions. c-met and VE-cadherin were shown to be inversely regulated by cell density, at both the protein and the mRNA levels. We established that c-met is up-regulated during the in vitro recapitulation of several steps of angiogenesis. The c-met expression was increased shortly after switching to angiogenic growth conditions and remained high during the very first steps of angiogenesis, including cell migration, and cell proliferation. The endothelial cells in which the expression of c-met was up-regulated were more responsive to HGF and exhibited a higher rate of morphogenesis. Moreover, the antibody directed against the extracellular domain of the c-met inhibited angiogenesis in vitro. Our results suggest that c-met is a marker of angiogenic phenotype for endothelial cells and represents an attractive target for the development of new antiangiogenic therapies.
Transforming growth factor-β1 down-regulates expression of chemokine stromal cell–derived factor-1: functional consequences in cell migration and adhesion
Authors: Wright Natalia , de Lera Teresa Laín , García-Moruja Carelia , Lillo Rosa , García-Sánchez Félix , Caruz Antonio , Teixidó Joaquin
Published: June 2003

Chemokine stromal cell–derived factor-1 (SDF-1) is expressed by bone marrow (BM) stromal cells and plays key roles in BM cell migration. Modulation of its expression could affect the migratory capacity of cells trafficking the BM, such as hematopoietic progenitor and leukemic cells. Transforming growth factor-β1 (TGF-β1) is present in the BM environment and constitutes a pivotal molecule controlling BM cell proliferation and differentiation. We used the BM stromal cell line MS-5 as a model to investigate whether SDF-1 expression constitutes a target for TGF-β1 regulation and its functional consequences. We show here that TGF-β1 down-regulates SDF-1 expression, both at the mRNA level, involving a decrease in transcriptional efficiency, and at the protein level, as detected in lysates and supernatants from MS-5 cells. Reduction of SDF-1 in supernatants from TGF-β1–treated MS-5 cells correlated with decreased, SDF-1–dependent, chemotactic, and transendothelial migratory responses of the BM model cell lines NCI-H929 and Mo7e compared with their responses to supernatants from untreated MS-5 cells. In addition, supernatants from TGF-β1–exposed MS-5 cells had substantially lower efficiency in promoting integrin α4β1–mediated adhesion of NCI-H929 and Mo7e cells to soluble vascular cell adhesion molecule-1 (sVCAM-1) and CS-1/fibronectin than their untreated counterparts. Moreover, human cord blood CD34+ hematopoietic progenitor cells displayed SDF-1–dependent reduced responses in chemotaxis, transendothelial migration, and up-regulation of adhesion to sVCAM-1 when supernatants from TGF-β1–treated MS-5 cells were used compared with supernatants from untreated cells. These data indicate that TGF-β1–controlled reduction in SDF-1 expression influences BM cell migration and adhesion, which could affect the motility of cells trafficking the bone marrow.
Intronic BCL-6 mutations are preferentially targeted to the translocated allele in t(3;14)(q27;q32) non-Hodgkin B-cell lymphoma
Authors: Jardin Fabrice , Bastard Christian , Contentin Nathalie , Parmentier Françoise , Picquenot Jean-Michel , Tilly Hervé , Stevenson Freda K. , Sahota Surinder S.
Published: June 2003

Translocations and somatic mutations are common genetic alterations of the BCL-6 gene on chromosome 3q27 in B-cell lymphoma, with implications for lymphomagenesis. The 2 events may have linked origins and can influence juxtaposed loci. To evaluate this further, we compared mutations occurring within the major mutation cluster region of the translocated and untranslocated BCL-6 alleles in 7 t(3;14)(q27;14q32) lymphomas. In 6 of 7 cases, the translocated allele revealed significantly higher mutations (mean, 5.8 × 10–2 bp–1) than did the untranslocated allele (mean, 5.3 × 10–3 bp–1; P < .01). The increase mapped to der(14q32), which retains the BCL-6 promoter and is transcriptionally active, as revealed by fusion transcripts and ongoing somatic mutations, absent in the der(3q27) region. These results indicate that enhanced mutational activity at the translocated allele may be a consequence of loss of cis regulatory elements or gain of IgH enhancer elements. Junctional sequences indicate translocation origins from earlier BCL-6 mutations and switch recombinase events.
Efficacy of imatinib mesylate in the treatment of idiopathic hypereosinophilic syndrome
Authors: Cortes Jorge , Ault Patricia , Koller Charles , Thomas Deborah , Ferrajoli Alessandra , Wierda William , Rios Mary B. , Letvak Laurie , Kaled Elizabeth S. , Kantarjian Hagop
Published: June 2003

Idiopathic hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterized by persistent eosinophilia and organ involvement. Different treatments have been investigated in HES with modest success. It has been suggested that imatinib is active in HES. We treated 9 patients with HES with 100 mg imatinib daily. Doses for patients without response after 4 weeks were increased to 400 mg daily. Prior therapy had failed for 7 patients. Five patients responded: 4 achieved sustained complete remission lasting a median of 12+ weeks (range, 9+ to 36+ weeks), and 1 had a transient response. One patient died in complete remission. Responses occurred within 4 weeks of therapy; only 1 responder required an increase in dose to 400 mg daily. Three of 4 nonresponders failed to respond to an increase in dose. Toxicity was minimal. We conclude that imatinib therapy is effective for HES.
MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223)
Authors: Andreae Susanne , Buisson Sandrine , Triebel Frédéric
Published: June 2003

On encountering a danger signal, dendritic cells (DCs) undergo a complex maturation process and become specialized in antigen presentation. We previously reported that engagement of major histocompatibility complex (MHC) class II molecules located on immature DCs in membrane rafts by lymphocyte activation gene-3 (LAG-3; CD223) leads to DC maturation. In contrast, exposure of DCs to class II–specific monoclonal antibodies (mAbs) did not lead to maturation. Here, we have investigated the signal transduction pathways involved in the LAG-3–induced maturation of human monocyte-derived DCs. We first show that areas of raft aggregation (both cholesterol rich and CDw78 microdomains) could be visualized using a soluble LAG-3 protein and confocal microscopy. Engagement of class II molecules by both its natural ligand LAG-3 and class II mAb induces rapid protein phosphorylation of phospholipase Cγ2 (PLCγ2) and p72syk as well as activation of phosphatidyl inositol 3-kinase/Akt, p42/44 extracellular signal-regulated protein kinase, and p38 mitogen-activated protein kinase pathways. Studies using inhibitors demonstrate that these 3 pathways are all important in inducing the maturation process of LAG-3–stimulated DCs. When class II molecules were ligated with LAG-3 versus specific antibody, differences in the phosphorylation pattern of c-Akt were observed. Thus, MHC class II signaling in DCs involves several pathways that have to be finely regulated to lead to cell activation and maturation.
Anergic T cells exert antigen-independent inhibition of cell-cell interactions via chemokine metabolism
Authors: James Martha J. , Belaramani Lavina , Prodromidou Kanella , Datta Arpita , Nourshargh Sussan , Lombardi Giovanna , Dyson Julian , Scott Diane , Simpson Elizabeth , Cardozo Lorraine , Warrens Anthony , Szydlo Richard M. , Lechler Robert I. , Marelli-Berg Federica M.
Published: June 2003

Due to their ability to inhibit antigen-induced T-cell activation in vitro and in vivo, anergic T cells can be considered part of the spectrum of immunoregulatory T lymphocytes. Here we report that both murine and human anergic T cells can impair the ability of parenchymal cells (including endothelial and epithelial cells) to establish cell-cell interactions necessary to sustain leukocyte migration in vitro and tissue infiltration in vivo. The inhibition is reversible and cell-contact dependent but does not require cognate recognition of the parenchymal cells to occur. Instrumental to this effect is the increased cell surface expression and enzymatic activity of molecules such as CD26 (dipeptidyl-peptidase IV), which may act by metabolizing chemoattractants bound to the endothelial/epithelial cell surface. These results describe a previously unknown antigen-independent anti-inflammatory activity by locally generated anergic T cells and define a novel mechanism for the long-known immunoregulatory properties of these cells.
Anti–third-party veto CTLs overcome rejection of hematopoietic allografts: synergism with rapamycin and BM cell dose
Authors: Bachar-Lustig Esther , Reich-Zeliger Shlomit , Reisner Yair
Published: June 2003

Several bone marrow cells and lymphocyte subpopulations, known as “veto cells,” were shown to induce transplantation tolerance across major histocompatibility antigens. Some of the most potent veto cells are of T-cell origin, and in particular a very strong veto activity was documented for cytotoxic T-lymphocyte (CTL) lines or clones. However, these cells also possess marked graft-versus-host (GVH) reactivity. In the present study we evaluated a new approach to deplete CTLs of antihost clones by stimulating the donor T cells against third-party stimulators in the absence of exogenous interleukin 2 (IL-2). We demonstrate that such CTLs are depleted of GVH reactivity while maintaining marked veto activity in vitro. Furthermore, marked synergism was exhibited between the veto CTLs and rapamycin when tested in a murine model, which measures T-cell–mediated bone marrow allograft rejection, or in sublethally irradiated allogeneic hosts.

Our results suggest that engraftment of early progenitors could be enhanced by using host-nonreactive anti–third-party CTLs, in conjunction with nonmyeloablative rapamycin-based conditioning protocols, thereby significantly reducing the toxicity of allogeneic transplantation.
Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex vivo
Authors: Jiang Shuiping , Camara Niels , Lombardi Giovanna , Lechler Robert I.
Published: June 2003

Although CD4+CD25+ regulatory T cells are pivotal in the prevention of autoimmunity and appear to mediate transplantation tolerance, little is known concerning their antigen specificity. Here we describe the induction of a human CD4+CD25+ regulatory T-cell line specific for a defined peptide alloantigen (human leukocyte antigen A2 [HLA-A2] 138-170) by priming purified CD4+CD25+ cells ex vivo. The regulatory cells were anergic and retained their ability to suppress antigen-driven responses of CD4+CD25– cells. They inhibited not only interleukin 2 (IL-2) secretion by CD4+CD25– T cells specific for the same peptide but also direct alloresponse of naive CD4+CD25– T cells stimulated by semiallogeneic dendritic cells (DCs) in the presence of the peptide (“linked suppression”). They also suppressed the response of CD4+ T cells specific for viral and bacterial antigens. The suppressive T-cell line showed sustained high CD25 expression. These findings suggest that peripheral CD4+CD25+ regulatory cells are a precommitted cell lineage from which cells with specificity for non–self-peptides can be selected. This may pave the way for inducing and expanding peptide antigen-specific regulatory T cells ex vivo for cell therapy in transplantation, allergy, and autoimmune disease.
Home recording of PEF in young asthmatics: does it contribute to management?
Authors: Uwyyed K , Springer C , Avital A , Bar-Yishay E , Godfrey S
Published: June 2003

The value of home monitoring of peak expiratory flow (PEF) as part of an action plan for asthma management in children and young adults is uncertain. We sought to determine whether home recording of PEF benefited asthma management and whether any contribution was affected by the severity of the asthma. Twenty-eight children and young adults with asthma of different severity (mean age 14 yrs; 95% confidence interval (95% CI) 12-16 yrs) recorded their symptoms, drug consumption and PEF twice daily for a mean of 82 days over a 12 week period, and attended the laboratory every 2 weeks for measurement of lung function. The number of individual patients with significant correlations for laboratory lung function tests compared with ambulatory PEF and diary scores averaged over the preceeding 2 weeks was low in all severity groups. When measured in the laboratory, PEF meter readings correlated poorly with PEF measured by spirometry. The proportion of patients with significant correlations for PEF, symptoms and rescue bronchodilator use on a day-to-day basis was 70-80% in the group of severe asthmatics and significantly less in the mild asthmatics. In a subgroup of 14 patients who were sick on a mean of 19 days, the mean difference in PEF between well and sick days was 14% of predicted. Diurnal PEF variation correlated poorly with other parameters in all groups. It is concluded that PEF monitoring adds little to daily recording of symptoms and bronchodilator use in the management of young patients with severe asthma, and it is too insensitive to register meaningful clinical changes in those with milder asthma.
Compliance with and accuracy of daily self-assessment of peak expiratory flows (PEF) in asthmatic subjects over a three month period
Authors: Verschelden P , Cartier A , L'Archeveque J , Trudeau C , Malo JL
Published: June 2003

Serial peak expiratory flow (PEF) assessment has been proposed in the clinical evaluation of asthma. In subjects attending the asthma clinic of a tertiary care hospital, we wanted to assess: 1) compliance in performing PEF; and 2) accuracy of a PEF-diary. Twenty adult asthmatic subjects, all using inhaled steroids, were asked to assess their PEF in the morning and evening with a VMX instrument (Clement Clarke Int., Colombus, OH, USA). This instrument, which incorporates a standard mini-Wright peak flow meter, stores PEF data on a computer chip. Subjects were not informed that the values were being stored. The mean duration of PEF monitoring was 89 days (range 44-131 days). For the total of 20 subjects, it was estimated that 3,482 values should have been written down and stored on the VMX computer chip. Whilst 1,897 values (54%) were written down, only 1,533 (44%) were stored, 425 values being invented. Morning and evening values were stored on 34% of days; and values were stored at least once a day on 55% of days. The values written down corresponded precisely to stored values 90% of the time, and were within +/- 20 L 94% of the time. We conclude that: 1) compliance with daily peak expiratory flow assessments is generally poor in chronic stable asthmatic subjects assessed on two visits separated by a 3 month period; and 2) a substantial percentage of values (22%) is invented. The unsatisfactory compliance with peak expiratory flow monitoring in this group of asthmatics on inhaled steroids underlines the need for similar studies on peak expiratory flow monitoring as part of an action treatment plan, and in more severe and brittle asthmatics.
Compliance with nedocromil sodium and a nedocromil sodium/salbutamol combination. Compliance Working Group
Authors: Braunstein GL , Trinquet G , Harper AE
Published: June 2003

Nonadherence to prescribed preventive medication is common in asthma. We wanted to assess whether the combination of a beta 2-bronchodilator with an anti-inflammatory treatment in the same metered-dose inhaler (MDI) with a regular dosing schedule might improve compliance. A double-blind study was used to compare use (two actuations four times daily for 12 weeks) of 2 mg nedocromil sodium (n = 101) with a combination of 2 mg nedocromil sodium and 100 micrograms salbutamol (n = 100) in mild-to-moderate asthma patients (mean age 42 +/- 14 yrs; 98 males and 103 females). Compliance was measured using the electronic Nebulizer Chronolog (NC) device, change in MDI canister weight, patient questionnaire and physician assessment. The mean +/- SD number of actuations per day for nedocromil sodium and the combination during the primary period of assessment (Weeks 11-12) was 4.2 +/- 2.6 and 4.6 +/- 2.5 (NC), 5.3 +/- 2.1 and 5.3 +/- 2.0 (canister weight), and 7.5 +/- 1.3 and 7.4 +/- 1.3 (questionnaire), respectively. Physician assessment rated compliance as "good" to "excellent". The first and final days of the period were not used in the NC analysis to exclude part-days of treatment and drug-dumping (repeated actuations without inhalation), and may account for the difference between NC and canister weight results. The mean number of two-actuation doses per day determined from the NC was 2.1 +/- 1.3 for nedocromil sodium and 2.4 +/- 2.1 for the combination. Thirty five percent (nedocromil sodium) and 34% (combination) of the patients were compliant (6-10 actuations per day for > or = 60% of the days). We conclude that compliance is poor in asthma, electronic recording revealed the dumping phenomenon and, in this study, the combination of an inhaled beta 2-bronchodilator with a preventive treatment did not improve compliance over a three month period in patients with mild-to-moderate asthma.
Comparison of early and late asthmatic responses between patients with allergic rhinitis and mild asthma
Authors: Bonavia M , Crimi E , Quaglia A , Brusasco V
Published: June 2003

Allergic rhinitic subjects without symptoms of asthma show airway hyperresponsiveness, but to a lesser degree than asthmatics. As airway responsiveness is a determinant of the bronchial response to allergen, rhinitic subjects should also respond to allergen challenge, but to a lesser extent than asthmatics. However, studies have so far failed to show quantitative differences in allergen responses between patients with rhinitis and patients with asthma. We studied 123 allergic subjects classified, on the basis of a scored symptom questionnaire, as follows: pure rhinitics without any symptom of asthma (Group 1, n = 39), true asthmatics with or without rhinitis (Group 2, n = 41), and subjects with borderline symptoms of asthma (Group 3, n = 43). All subjects underwent both methacholine and allergen inhalation challenges, with pollen challenges performed out of season. When the three groups were pooled, the asthma symptom score was directly correlated with the sensitivities both to methacholine and allergen, whilst both the sensitivity to allergen and the severity of late-phase response were correlated with the sensitivity to methacholine. The percentage of subjects with a positive early-phase asthmatic response to allergen was similar in Groups 1 and 2. Group 2 had higher sensitivities both to methacholine and to allergen than Group 1. A late-phase asthmatic response occurred more frequently in Group 2 than in Group 1, and this difference was due to a higher occurrence of late-phase response in subjects allergic to house dust mite in Group 2. This study confirms that the bronchial response to allergen can be predicted, in rhinitic as well as in asthmatic allergic subjects, on the basis of airway responsiveness to methacholine. We conclude that the presence or the absence of asthma symptoms in allergic subjects may be related to a quantitatively different airway responsiveness to allergen.
Acceptance and long-term compliance with nCPAP in patients with obstructive sleep apnoea syndrome
Authors: Pieters T , Collard P , Aubert G , Dury M , Delguste P , Rodenstein DO
Published: June 2003

Previous studies have generally shown poor effective long-term compliance with nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnoea syndrome (OSAS). We performed a retrospective study of patients treated with nCPAP for more than one year. Compliance was defined as the average number of hours of nCPAP use per day, where hours of use were obtained from the built-in time counter of the nCPAP device, after deduction of the 10% difference between effective use and time counters previously shown by others. We present data on the first 95 patients for whom results were available. The follow-up period was 784 +/- 366 (mean +/- SD) days for the whole group. Compliance was 5 +/- 1.8 h. For a subgroup of 36 patients, we had data on two consecutive follow-up periods (673 +/- 235 and 390 +/- 147 days for the first and second period, respectively). Compliance remained stable (5.2 +/- 1.5 and 5 +/- 2.3 h, respectively). For the whole group, a significant correlation was found between compliance and sleep fragmentation expressed as the movement arousal index (r = 0.226). During a similar 3 year period, 155 patients with a confirmed diagnosis of OSAS were offered a nCPAP trial. CPAP was actually delivered for home use to 117 patients (76%). During this same 3 year period, only 21 patients out of a total of 192 followed-up in our institution quit treatment, mainly due to intolerance or cure. These results indicate that in a nonselected group of obstructive sleep apnoea syndrome patients a high and stable compliance with nasal continuous positive pressure can be achieved, contradicting recent results of other series.
Differential effects of nasal continuous positive airway pressure on reversible or fixed upper and lower airway obstruction
Authors: Wang CH , Lin HC , Huang TJ , Yang CT , Yu CT , Kuo HP
Published: June 2003

Our study was to assess whether there were differential effects of nasal continuous positive airway pressure (nCPAP) on different kinds of obstruction in either upper or lower airways in patients with chronic obstructive pulmonary disease (COPD). nCPAP (6 cmH2O for ten minutes) was applied to 7 patients with reversible extrathoracic upper airway obstruction (RUAO) and 3 patients with fixed extrathoracic upper airway obstruction (FUAO). Eighteen stable asthmatics, receiving methacholine challenge to induce a more than 20% reduction in FEV1, were randomly investigated for the effect of nCPAP or sham pressure on reversible lower airway obstruction. Nine stable COPD patients were enrolled to study the effect on irreversible lower airway obstruction. Maximal expiratory and inspiratory flow volume curves and dyspnoea scores were obtained before and after immediate withdrawal of nCPAP. In the RUAO group, nCPAP significantly improved stridor and dyspnoea scores, decreased the ratio of FEF50/FIF50 from 2.05 +/- 0.25 to 1.42 +/- 0.16, and increased peak inspiratory flow (PIF) as well as forced inspiratory vital capacity by 26 +/- 8% and 9 +/- 4%, respectively. In expiratory phase, there was no significant change in pulmonary functions. In asthmatics, nCPAP significantly reversed methacholine-induced bronchoconstriction increasing forced vital capacity by 10 +/- 3%, FEV1 by 15 +/- 4% and PIF by 32 +/- 11%. nCPAP significantly increased the response to bronchodilators. The improvement in airflow rate persisted for at least 5 min after nCPAP withdrawal and was highly correlated with the response to bronchodilators. There was no significant effect of nCPAP on airflow rate in COPD patients. Subjective dyspnoea score changes paralleled the pulmonary function improvement. We conclude that there are differential effects of nCPAP on airflow rates in patients with different nature of airway obstruction. Patients with airway obstruction caused by structural changes may not benefit from the use of nCPAP in improving airflow rates.
Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease
Authors: Krombach F , Gerlach JT , Padovan C , Burges A , Behr J , Beinert T , Vogelmeier C
Published: June 2003

This flow cytometric study was designed to identify, characterize and quantify alveolar monocyte-like cells in healthy volunteers and in patients with chronic inflammatory lung disease. Cells were obtained by bronchoalveolar lavage (BAL) from 19 patients with sarcoidosis, 29 with idiopathic pulmonary fibrosis, 10 with extrinsic allergic alveolitis, 19 with collagen vascular disease, and from 10 healthy volunteers. By taking advantage of the distinct electro-optical features of alveolar macrophages (AMs) and monocyte-like cells, the numbers of alveolar monocyte-like cells were counted, the cell dimensions calculated, and the densities of antigens on the surface of alveolar monocyte-like cells and AMs were compared. By using a panel of monoclonal antibodies detecting CD11b, CD14, CD16, and human leucocyte antigen-DR (HLA-DR), the immunophenotypes of these cells were selectively characterized. In the BAL fluid of patients with chronic inflammatory lung disease, significantly increased numbers of alveolar monocyte-like cells were detected that exhibited an immunophenotype intermediate between blood monocytes and mature AMs. Positive correlations were found between numbers of monocyte-like cells and expression of the monocyte-associated surface antigens CD11b and CD14 on total AMs; in contrast, an inverse relationship existed between monocyte numbers and expression of the macrophage-associated surface antigens CD16 and HLA-DR. When the patients were assigned to two groups according to the percentage of BAL monocyte-like cells being lower or higher than 13% (= mean value of the controls +2SD), it could be demonstrated that a high percentage of BAL monocyte-like cells was associated with significantly reduced lung function parameters. In summary, our flow cytometric data strongly support the view that considerable numbers of blood monocytes are recruited to the bronchoalveolar space in patients with chronic inflammatory lung disease.
Neutrophil activation in fibrosing alveolitis: a comparison of lone cryptogenic fibrosing alveolitis and systemic sclerosis
Authors: Cailes JB , O'Connor C , Pantelidis P , Southcott AM , Fitzgerald MX , Black CM , du Bois RM
Published: June 2003

Fibrosing alveolitis complicating systemic sclerosis (FASSc) carries a better prognosis than lone cryptogenic fibrosing alveolitis (CFA). We wanted to determine whether this improved prognosis is associated with differential neutrophil migration and activation in the lower respiratory tract. We therefore compared bronchoalveolar lavage (BAL) neutrophil numbers and levels of neutrophil-derived enzymes in FASSc, CFA and normal individuals. Bronchoalveolar lavage was performed on 45 subjects (FASSc n = 20; CFA n = 15; normals n = 10); cell counts and levels of neutrophil-derived enzymes, myeloperoxidase, elastase (total elastase and elastase/alpha 1 antitrypsin complexes), collagenase and lactoferrin were measured. Lung function testing was performed in subjects with fibrosing alveolitis. Significant differences in the levels of collagenase, myeloperoxidase and elastase/ alpha 1-antitrypsin complexes were present in the BAL fluid from the three groups. Patients with CFA had significantly higher neutrophil percentages and levels of collagenase and myeloperoxidase than those with FASSc. Disease extent, as judged by lung volumes and gas transfer, was comparable in the CFA and FASSc groups. Forced vital capacity (% predicted) was significantly lower in patients with evidence of increased neutrophil enzyme release than those without. We conclude that: 1) increased neutrophil migration to the lung is accompanied by release both of primary and secondary granule enzymes in cryptogenic fibrosing alveolitis; and 2) the lower amounts of neutrophil products in fibrosing alveolitis complicating systemic sclerosis may account for the improved prognosis, even when disease is as extensive as in cryptogenic fibrosing alveolitis.
Effect of long-term primary aerosolized pentamidine prophylaxis on breakthrough Pneumocystis carinii pneumonia
Authors: Ewig S , Schafer H , Rockstroh JK , Pickenhain A , Luderitz B
Published: June 2003

Aerosolized pentamide is a well-tolerated primary prophylaxis regimen for Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. It is now commonly administered for prolonged periods. We therefore studied the effect of long-term inhalation on breakthrough PCP. We recorded clinical, immunological, radiological and microbiological data, as well as therapy and clinical course of all episodes with confirmed PCP diagnosed at our institution between January 1, 1990 and June 30, 1995. Furthermore, data of all patients on primary aerosolized pentamidine since May 1, 1989 were retrieved. Prophylaxis failures were subdivided into "early" (< or = 12 months of inhalation time) and "late" (> 12 months of inhalation time) failures and were compared with episodes without any prophylaxis. Thirty patients without any prophylaxis, six with early and 14 with late failures represented the study population. Mean +/- SD inhalation times were 4.9 +/- 4.8 and 26.3 +/- 14.1 months, respectively. No significant differences could be detected with regard to clinical presentation, severity of PCP, and in-hospital as well as long term outcome. Early as well as late prophylaxis failures had a higher incidence of upper lobe infiltrates on chest radiography (50% without prophylaxis versus 100% with early and 83% with late failure, respectively; p < 0.05). No extrapulmonary or disseminated pneumocystosis was observed in either group. The sensitivity of site-directed bronchoalveolar lavage was conserved after long-term inhalation (86% versus 100% without prophylaxis and 97% in early failure; p = NS). The severity and outcome of Pneumocystis carinii pneumonia is not altered by long-term primary aerosolized pentamidine prophylaxis. Presentation with upper lobe infiltrates is a radiographic pattern also of late failures. Bronchoalveolar lavage should, therefore, be performed using the site-directed technique in this setting.
Pleuropulmonary changes induced by ergoline drugs
Authors: Pfitzenmeyer P , Foucher P , Dennewald G , Chevalon B , Debieuvre D , Bensa P , Piard F , Camus P
Published: June 2003

Classic ergolines, such as bromocriptine, methysergide and ergotamine, can induce chronic pleuropneumonitis. We present the cases of eight patients who developed similar changes whilst on other ergolines. In this retrospective case study spanning 1985-1995, clinical data, radiological material, pulmonary function, bronchoalveolar lavage and histopathology were reviewed. Earlier literature on ergoline-induced pleuropulmonary changes was reviewed. Eight middle-aged to elderly individuals of both sexes developed pleuropulmonary changes during long-term therapy with regular dosages of nicergoline (n = 4), dihydroergocristine (n = 3), or dihydroergotamine (n = 1). Bibasilar pleural thickening with or without pleural effusion was present on chest radiographs and computed tomographic (CT) scans in six cases. Increased erythrocyte sedimentation rate was seen in most. Pure interstitial pneumonitis developed in two patients on dihydroergocristine and was reversible in each. Bronchoalveolar lavage was performed in four cases and was abnormal in all, but demonstrated no consistent pattern. Most patients exhibited lung restriction. The outcome was favourable showing slow improvement in all cases following discontinuation of the ergoline. Slight residual pleural thickening was seen in five out of the six cases with pleural involvement. Nicergoline and dihydroergotamine can induce a syndrome of chronic pleural thickening/effusion that slowly improves after drug withdrawal. Dihydroergocristine can induce reversible interstitial pneumonitis.
Epidemiological studies of the respiratory effects of air pollution
Authors: Lebowitz MD
Published: June 2003

Environmental epidemiological studies of the health effects of air pollution have been major contributors to the understanding of such effects. The chronic effects of atmospheric pollutants have been studied, but, except for the known respiratory effects of particulate matter (PM), they have not been studied conclusively. There are ongoing studies of the chronic effects of certain pollutant classes, such as ozone, acid rain, airborne toxics, and the chemical form of PM (including diesel exhaust). Acute effects on humans due to outdoor and indoor exposures to several gases/fumes and PM have been demonstrated in epidemiological studies. However, the effects of these environmental factors on susceptible individuals are not known conclusively. These acute effects are especially important because they increase the human burden of minor illnesses, increase disability, and are thought to decrease productivity. They may be related to the increased likelihood of chronic disease as well. Further research is needed in this latter area, to determine the contributions of the time-related activities of individuals in different microenvironments (outdoors, in homes, in transit). Key elements of further studies are the assessment of total exposure to the different pollutants (occurring from indoor and outdoor source) and the interactive effects of pollutants. Major research areas include determination of the contributions of indoor sources and of vehicle emissions to total exposure, how to measure such exposures, and how to measure human susceptibility and responses (including those at the cellular and molecular level). Biomarkers of exposures, doses and responses, including immunochemicals, biochemicals and deoxyribonucleic acid (DNA) adducts, are beginning to promote some basic knowledge of exposure-response, especially the mechanisms. These will be extremely useful additions to standard physiological, immunological, and clinical instruments, and the understanding of biological plausibility. The outcomes of all this work will be the management of risks and the prevention of respiratory diseases related to air pollution.
Computed tomography in adult respiratory distress syndrome: what has it taught us?
Authors: Pelosi P , Crotti S , Brazzi L , Gattinoni L
Published: June 2003

Computed tomography (CT) has played an important role in improving our knowledge of the pathophysiology of the adult respiratory distress syndrome (ARDS), and in determining the morphological and functional relationships of different manoeuvres commonly used in the therapeutic management of this syndrome (changes in body position, application of positive end-expiratory pressure (PEEP) and mechanical ventilation). During the early phase of the disease, the ARDS lung is characterized by a homogenous alteration of the vascular permeability. Thus, oedema accumulates evenly in all lung regions with a nongravitational distribution (homogenous lung). The increased lung weight, due to increased oedema, causes a collapse of the lung regions along the vertical axis, through the transmission of hydrostatic forces (compression atelectasis). Thus, the lesions appear mainly in the dependent lung regions (dishomogeneous lung). During inspiration, at plateau pressure, the pulmonary units reopen and, if the PEEP applied is adequate, they stay open during the following expiration. Adequate PEEP is equal to or higher than the hydrostatic forces compressing that unit. Prone position is another manoeuvre which allows previously collapsed lung regions to reopen and, conversely, compresses previously aerated regions, reversing the distribution of gravitational forces. During late ARDS, there is less compression atelectasis and the lung undergoes structural changes, due to the reduced amount of oedema. This is usually associated with CO2 retention and the development of emphysema-like lesions. In conclusion, computed tomography is not only a research tool, but a useful technique which allows a better understanding of the progressive change in strategy needed to ventilate the adult respiratory distress syndrome lung at different stages of the disease.
Oesophageal reflux and asthma
Authors: Ayres JG , Miles JF
Published: June 2003

Asthma and gastro-oesophageal reflux commonly occur together but the association in any individual may or may not be causal. Aspiration of gastric acid into the trachea has been demonstrated in some patients with asthma with concomitant falls in lung function, while acid in the lower oesophagus can exacerbate asthma by a vagal reflex following stimulation of lower oesophageal receptors. Conversely, asthma can lead to worsening reflux both through the use of smooth muscle relaxing anti-asthma medication and by the mechanical effects of hyperinflation reducing lower oesophageal sphincter pressures. The effects on asthma following treatment of reflux has been anecdotally reported to be successful in some individuals, particularly those with severe reflux, but surgery should be reserved for individuals only after failure of medical treatment and should be aimed at improving reflux symptoms rather than improving asthma control.
A new correction technique for measuring respiratory impedance through an endotracheal tube
Authors: Lorino AM , Beydon L , Mariette C , Dahan E , Lorino H
Published: June 2003

Measurement of respiratory impedance (Zrs) in intubated patients requires corrections for flow-dependent resistance and air compression inside the endotracheal tube (ET). The purpose of this study was to test a new correction technique for these effects. We therefore studied 110 patients in two conditions: breathing normally (C1), or breathing through an ET placed at the mouth (C2). In C1, we measured pressure and flow signals at the mouth, and in C2, at the ET inlet, during application of a pseudorandom forced excitation (4-32 Hz). In C1, respiratory impedance was calculated directly as Z1. In C2, pressure data were first corrected for the flow-dependent resistance of the ET, and respiratory impedance was then corrected both for gas compression inside the set-up and ET inertance (impedance Z2). Strong linear relationships were found between the reference and corrected estimates of the resistance at 6 Hz, the frequency dependence of resistance and the resonant frequency. The mean normalized distance between Z1 and Z2 observed in the patients over the 4-32 Hz frequency range was about 14% for resistance and 12% for reactance (-9% and -4%, respectively, when considering the algebraic value of the distance). This slight underestimation of both components of impedance might be due to an overcorrection of pressure for the flow-dependent resistance of the ET. We conclude that, in intubated patients, newly tested corrections for the mechanical contribution of the endotracheal tube may yield a fair estimate of respiratory impedance when pressure is measured at the inlet of the endotracheal tube.
Tumour necrosis factor-alpha gene expression by alveolar macrophages in human lung allograft recipient with recurrence of sarcoidosis. Toulouse Lung Transplantation Group
Authors: Martel S , Carre PC , Carrera G , Pipy B , Leophonte PJ
Published: June 2003

Recurrence of sarcoidosis in lung allografts is an interesting model to study the pathogenesis of this disease. We report a case of sarcoidosis recurrence in a single lung allograft recipient 2 years after transplantation. The expression of tumour necrosis factor-alpha (TNF-alpha) gene by alveolar macrophages was monitored. The TNF-alpha gene was not expressed at the time of recurrence of sarcoidosis, but only later when prominent granulomas were observed.
Reactive airways dysfunction syndrome (RADS) following exposure to toxic gases of a swine confinement building
Authors: Cormier Y , Coll B , Laviolette M , Boulet LP
Published: June 2003

We describe the case of a 58 year old male, who developed a reactive airways dysfunction syndrome (RADS) after exposure to a high level of toxic gases in a swine confinement building. This previously healthy, nonatopic man developed moderate, partially reversible, airway obstruction and increased responsiveness within a month after the toxic exposure. The circumstances of the incident and the concomitant death of two sows make it likely that hydrogen sulphide was the causative agent. To our knowledge, this is the first case of reactive airways dysfunction syndrome reported from swine confinement buildings and, therefore, should raise awareness of this potential risk in that work environment.
Surveillance of tuberculosis in Europe. Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) for uniform reporting on tuberculosis cases
Authors: Rieder HL , Watson JM , Raviglione MC , Forssbohm M , Migliori GB , Schwoebel V , Leitch AG , Zellweger JP
Published: June 2003

Consensus-based recommendations have been developed by a Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) on uniform reporting of tuberculosis surveillance data in the countries of Europe. A uniform case definition and a minimum set of variables for reporting on each case have been agreed which, when collated on a national basis, will allow comparison of the epidemiology of tuberculosis in different European countries. The Working Group recommends that the case definition includes "definite" cases, where the diagnosis has been confirmed by culture (or supported by microscopy findings in countries where diagnostic culture facilities are not available), and "other than definite cases" based on a clinical diagnosis of tuberculosis combined with the intention to treat with a full course of antituberculosis therapy. Both "definite" and "other than definite" cases should be notified by physicians and, in addition, laboratories should be required to report "definite" cases. The minimum set of variables to be collected on each case of tuberculosis should include: date of starting treatment, place of residence, date of birth, gender, and country of origin, to characterize the patient. Recommended disease-specific variables include: site of disease, bacteriological status (microscopy and culture), and history of previous antituberculosis chemotherapy. The minimum set of variables should be collated on all patients and should be as complete as possible. Additional variables may be collected for individual, local or national purposes, but, in general, completeness of reporting on cases is likely to be better if the information requested is kept to a minimum. Timely reporting of cases is essential for appropriate public health action. Cases should be reported to the health authority at the local and/or regional level within 1 week of starting treatment. Individual-case based information should be reported to the national level by the local or regional level. Feedback to reporters is essential. At the national level, preliminary quarterly reports should be produced and final reports should be published annually.
Acid–base status of critically ill patients with acute renal failure: analysis based on Stewart–Figge methodology
Authors: Rocktaeschel Jens , Morimatsu Hiroshi , Uchino Shigehiko , Goldsmith Donna , Poustie Stephanie , Story David , Gutteridge Geoffrey , Bellomo Rinaldo
Published: June 2003

Introduction

The aim of the present study is to understand the nature of acid–base disorders in critically ill patients with acute renal failure (ARF) using the biophysical principles described by Stewart and Figge. A retrospective controlled study was carried out in the intensive care unit of a tertiary hospital.

Materials and methods

Forty patients with ARF, 40 patients matched for Acute Physiology and Chronic Health Evaluation II score (matched control group), and 60 consecutive critically ill patients without ARF (intensive care unit control group) participated. The study involved the retrieval of biochemical data from computerized records, quantitative biophysical analysis using the Stewart–Figge methodology, and statistical comparison between the three groups. We measured serum sodium, potassium, magnesium, chloride, bicarbonate, phosphate, ionized calcium, albumin, lactate and arterial blood gases.

Results

Intensive care unit patients with ARF had a mild acidemia (mean pH 7.30 ± 0.13) secondary to metabolic acidosis with a mean base excess of -7.5 ± 7.2 mEq/l. However, one-half of these patients had a normal anion gap. Quantitative acid–base assessment (Stewart–Figge methodology) revealed unique multiple metabolic acid–base processes compared with controls, which contributed to the overall acidosis. The processes included the acidifying effect of high levels of unmeasured anions (13.4 ± 5.5 mEq/l) and hyperphosphatemia (2.08 ± 0.92 mEq/l), and the alkalinizing effect of hypoalbuminemia (22.6 ± 6.3 g/l).

Conclusions

The typical acid–base picture of ARF of critical illness is metabolic acidosis. This acidosis is the result of the balance between the acidifying effect of increased unmeasured anions and hyperphosphatemia and the lesser alkalinizing effect of hypoalbuminemia.