bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Possible Neural Architectures Underlying Information-Geometric Measures
Authors: Tatsuno Masami , Okada Masato
Published: March 2004

A novel analytical method based on information geometry was recently proposed, and this method may provide useful insights into the statistical interactions within neural groups. The link between information-geometric measures and the structure of neural interactions has not yet been elucidated, however, because of the ill-posed nature of the problem. Here, possible neural architectures underlying information-geometric measures are investigated using an isolated pair and an isolated triplet of model neurons. By assuming the existence of equilibrium states, we derive analytically the relationship between the information-geometric parameters and these simple neural architectures. For symmetric networks, the first- and second-order information-geometric parameters represent, respectively, the external input and the underlying connections between the neurons provided that the number of neurons used in the parameter estimation in the log-linear model and the number of neurons in the network are the same. For asymmetric networks, however, these parameters are dependent on both the intrinsic connections and the external inputs to each neuron. In addition, we derive the relation between the information-geometric parameter corresponding to the two-neuron interaction and a conventional cross-correlation measure. We also show that the information-geometric parameters vary depending on the number of neurons assumed for parameter estimation in the log-linear model. This finding suggests a need to examine the information-geometric method carefully. A possible criterion for choosing an appropriate orthogonal coordinate is also discussed. This article points out the importance of a model-based approach and sheds light on the possible neural structure underlying the application of information geometry to neural network analysis.
Robustifying AdaBoost by Adding the Naive Error Rate
Authors: Takenouchi Takashi , Eguchi Shinto
Published: March 2004

AdaBoost can be derived by sequential minimization of the exponential loss function. It implements the learning process by exponentially reweighting examples according to classification results. However, weights are often too sharply tuned, so that AdaBoost suffers from the nonrobustness and overlearning. We propose a new boosting method that is a slight modification of AdaBoost. The loss function is defined by a mixture of the exponential loss and naive error loss functions. As a result, the proposed method incorporates the effect of forgetfulness into AdaBoost. The statistical significance of our method is discussed, and simulations are presented for confirmation.
Boosting with Noisy Data: Some Views from Statistical Theory
Authors: Jiang Wenxin
Published: March 2004

This letter is a comprehensive account of some recent findings about AdaBoost in the presence of noisy data when approached from the perspective of statistical theory. We start from the basic assumption of weak hypotheses used in AdaBoost and study its validity and implications on generalization error. We recommend studying the generalization error and comparing it to the optimal Bayes error when data are noisy. Analytic examples are provided to show that running the unmodified AdaBoost forever will lead to overfit. On the other hand, there exist regularized versions of AdaBoost that are consistent, in the sense that the resulting prediction will approximately attain the optimal performance in the limit of large training samples.
An Extended Projection Neural Network for Constrained Optimization
Authors: Xia Youshen
Published: March 2004

Recently, a projection neural network has been shown to be a promising computational model for solving variational inequality problems with box constraints. This letter presents an extended projection neural network for solving monotone variational inequality problems with linear and nonlinear constraints. In particular, the proposed neural network can include the projection neural network as a special case. Compared with the modified projection-type methods for solving constrained monotone variational inequality problems, the proposed neural network has a lower complexity and is suitable for parallel implementation. Furthermore, the proposed neural network is theoretically proven to be exponentially convergent to an exact solution without a Lipschitz condition. Illustrative examples show that the extended projection neural network can be used to solve constrained monotone variational inequality problems.
The Simplest Surrealist Act: Valerie Solanas and the (Re) Assertion of Avantgarde Priorities
Authors: Harding James M.
Published: March 2004

She shot pop art superstar Andy Warhol—but, really, who was Valerie Solanas? And what was “SCUM”? Answering those questions tells a lot about the radically changing landscape of the American avantgarde of the late 1960a.
“No Joke in Petticoats”: British Polar Expeditions and Their Theatrical Presentations
Authors: Pearson Mike
Published: March 2004

By late March 1902, the British National Antarctic Expedition's ship Discovery was frozen in. Atop the ice, the explorers erected a hut, which was fitted with a stage, scenery, and footlights. The Royal Terror Theatre opened in June with Ticket-of-Leave and climaxed in August with a minstrel show. In the icy darkness white men played women and black men, parodied and critiqued structures of power, reinforced attitudes of racial prejudice, and labored at activities that saved their sanity if not their lives. The prolonged engagement in play challenges the easy narrative of courage, endurance, and heroic survival usually associated with polar expeditions.
Jackson Pollock's Post-Ritual Performance: Memories Arrested in Space
Authors: Soussloff Catherine M.
Published: March 2004

Uneasy that Jackson Pollock's paintings indicate a profound involvement with myth and that his dedication to the curative potential of psychoanalysis indicate a sustained engagement with his infantile fantasies and early family history, art historians have not agreed on how to interpret Pollock's paintings. There are two major trends: Pollock's “opticality” and the meaning of the nonrepresentational and representational marks found in them. Soussloff seeks a third way—the meaning of myth, ritual, and performance in Pollock's abstractions.
Jin Xing in the New China: Redefining the Mainstream
Authors: Kimbrough Andrew
Published: March 2004

Among the five modern dance companies in China, Jin Xing's is perhaps the best known. In her choreography, Jin Xing suffuses a distinctly Western form with a unique Chinese perspective. But Jin Xing's fame arises not only from her choreography but from her sex-change operation, performed in Beijing in 1995. In this interview, Jin Xing explores all aspects of her work in a system where a decidedly unencouraging government keeps a close eye on public performances.
Somewhere, Over the Rainbow: White-Female-Canadian Dramaturge in Cape Town
Authors: Rudakoff Judith
Published: March 2004

In post-apartheid South Africa, economic inequity between the races, street violence, rivalries between the African National Congress and the Inkatha Freedom Party, and the AIDS pandemic continue to vex the nation. In this context, the larger narratives of apartheid and colonialism are joined by personal narratives of individual discovery. The result is theatre that is finding new forms, performance situations, and audiences.
Legal safeguards against medical practice by not suitably qualified persons: A comparative study in seven EU-countries
Authors: de Bijl  , Nederveen-van de Kragt
Published: March 2004

In this article the conditions and regulatory systems for access to medical practice in seven countries of the European Union are described with a view to the health protection of patients/consumers. In Belgium and France the legislator has chosen a monopolistic approach to the licensing of medical doctors: only the practice of medicine by legally qualified doctors is lawful. In Germany, Ireland and the United Kingdom a more tolerant system is in force: only medical practitioners with a university degree in medicine are recognized, but also persons who practice 'alternative medicine' without a medical degree are tolerated by law. In Denmark and the Netherlands the system is a mixture of the monopolistic and tolerant system. In principle everyone is allowed to practice medicine, with the exclusion of certain procedures that are reserved to qualified medical doctors. Violation of this limited monopoly can be prosecuted. The restrictions to and preconditions for access to medical practice are compared as well as the maintenance of the respective systems. The role of the legislator is described. From the perspective of the protection of patient's health and safety it seems that a mixed system offers the patient optimal protection.
Post Mortem assisted Procreation according to French Law
Authors: Mémeteau
Published: March 2004

No Abstract
Book Review
Authors: Guillod
Published: March 2004

No Abstract
Post mortem insemination
Authors: Hendriks
Published: March 2004

No Abstract
R v Human Fertilisation and Embryology Authority ex parte Blood, 6 February 1997.
Authors: Douglas
Published: March 2004

No Abstract
Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia
Authors: Aras Omer , Shet Arun , Bach Ronald R. , Hysjulien Jessica L. , Slungaard Arne , Hebbel Robert P. , Escolar Gines , Jilma Bernd , Key Nigel S.
Published: March 2004

The precise role of intravascular tissue factor (TF) remains poorly defined, due to the limited availability of assays capable of measuring circulating TF procoagulant activity (PCA). As a model of inflammation-associated intravascular thrombin generation, we studied 18 volunteers receiving an infusion of endotoxin. A novel assay that measures microparticle (MP)-associated TF PCA from a number of cellular sources (but not platelets) demonstrated an 8-fold increase in activity at 3 to 4 hours after endotoxin administration (P < .001), with a return to baseline by 8 hours. TF antigen-positive MPs isolated from plasma were visualized by electron microscopy. Interindividual MP-associated TF response to lipopolysaccharide (LPS) was highly variable. In contrast, a previously described assay that measurestotal (cell and MP-borne) whole-blood TF PCA demonstrated a more modest increase, with a peak in activity (1.3-fold over baseline; P < .000 01) at 3 to 4 hours, and persistence for more than 24 hours. This surprisingly modest increase in whole-blood TF activity is likely explained by a profound although transient LPS-induced monocytopenia. MP-associated TF PCA was highly correlated with whole-blood TF PCA and total number of circulating MPs, and whole-blood TF PCA was highly correlated with TF mRNA levels. (Blood. 2004;103:4545-4553)
The sphingosine 1-phosphate receptor agonist FTY720 supports CXCR4-dependent migration and bone marrow homing of human CD34+ progenitor cells
Authors: Kimura Takafumi , Boehmler Andreas M. , Seitz Gabriele , Kuçi Selim , Wiesner Tina , Brinkmann Volker , Kanz Lothar , Möhle Robert
Published: March 2004

The novel immunosuppressant FTY720 activates sphingosine 1-phosphate receptors (S1PRs) that affect responsiveness of lymphocytes to chemokines such as stromal cell-derived factor 1 (SDF-1), resulting in increased lymphocyte homing to secondary lymphoid organs. Since SDF-1 and its receptor CXCR4 are also involved in bone marrow (BM) homing of hematopoietic stem and progenitor cells (HPCs), we analyzed expression of S1PRs and the influence of FTY720 on SDF-1/CXCR4-mediated effects in human HPCs. By reverse transcriptase-polymerase chain reaction (RT-PCR), S1PRs were expressed in mobilized CD34+ HPCs, particularly in primitive CD34+/CD38- cells. Incubation of HPCs with FTY720 resulted in prolonged SDF-1-induced calcium mobilization and actin polymerization, and substantially increased SDF-1-dependent in vitro transendothelial migration, without affecting VLA-4, VLA-5, and CXCR4 expression. In nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice, the number of CD34+/CD38- cells that homed to the BM after 18 hours was significantly raised by pretreatment of animals and cells with FTY720, tending to result in improved engraftment. In addition, in vitro growth of HPCs (week-5 cobblestone area-forming cells [CAFCs]) was 2.4-fold increased. We conclude that activation of S1PRs by FTY720 increases CXCR4 function in HPCs both in vitro and in vivo, supporting homing and proliferation of HPCs. In the hematopoietic microenvironment, S1PRs are involved in migration and maintenance of HPCs by modulating the effects of SDF-1. (Blood. 2004;103:4478-4486)
Complications of β-thalassemia major in North America
Authors: Cunningham Melody J. , Macklin Eric A. , Neufeld Ellis J. , Cohen Alan R. ,   the Thalassemia Clinical Research Network
Published: March 2004

Treatment of patients with β-thalassemia major has improved dramatically during the past 40 years; however, the current clinical status of these patients remains poorly characterized. We performed a cross-sectional study of 342 patients in the Registry of the National Institutes of Health-sponsored Thalassemia Clinical Research Network. Evidence of hepatitis C exposure was present in 35% of tested patients, was associated with age, and had a rate of spontaneous viral clearance of 33%. Ferritin levels ranged from 147 to 11 010 ng/mL (median, 1696 ng/mL). Median hepatic iron content was 7.8 mg/g dry weight and 23% of patients had values of 15 mg/g dry weight or higher. No patients 15 years or younger and 5% of patients aged 16 to 24 years had heart disease requiring medication. Ten percent had cirrhosis on biopsy. Endocrinologic complications were common among adults. Seventy-four (22%) patients had recent implantable central venous access devices (CVADs) placed. Among 80 episodes of bacteremia in 38 patients, 90% were attributable to the CVAD. Among 330 patients who had received deferoxamine chelation therapy, 224 (68%) reported no complications. We conclude that hepatitis C, iron-related organ dysfunction, and complications of iron chelation therapy are strongly age-dependent in North American patients with β-thalassemia.
Graft-versus-leukemia in a retrovirally induced murine CML model: mechanisms of T-cell killing
Authors: Matte Catherine C. , Cormier James , Anderson Britt E. , Athanasiadis Ioanna , Liu Jinli , Emerson Stephen G. , Pear Warren , Shlomchik Warren D.
Published: March 2004

The graft-versus-leukemia (GVL) effect, mediated by donor T cells, has revolutionized the treatment of leukemia. However, effective GVL remains difficult to separate from graft-versus-host disease (GVHD), and many neoplasms are GVL resistant. Murine studies aimed at solving these problems have been limited by the use of leukemia cell lines with limited homology to human leukemias and by the absence of loss-of-function leukemia variants. To address these concerns, we developed a GVL model against murine chronic-phase chronic myelogenous leukemia (mCP-CML) induced with retrovirus expressing the bcr-abl fusion cDNA, the defining genetic abnormality of chronic-phase CML (CP-CML). By generating mCP-CML in gene-deficient mice, we have studied GVL T-cell effector mechanisms. mCP-CML expression of Fas or tumor necrosis factor (TNF) receptors is not required for CD8-mediated GVL. Strikingly, maximal CD4-mediated GVL requires cognate interactions between CD4 cells and mCP-CML cells as major histocompatibility complex-negative (MHC II-/-) mCP-CML is relatively GVL resistant. Nevertheless, a minority of CD4 recipients cleared MHC II-/- mCP-CML; thus, CD4 cells can also kill indirectly. CD4 GVL did not require target Fas expression. These results suggest that CPCML's GVL sensitivity may in part be explained by the minimal requirements for T-cell killing, and GVL-resistance may be related to MHC II expression. (Blood. 2004;103:4353-4361)
Deficient MHC class I cross-presentation of soluble antigen by murine neonatal dendritic cells
Authors: Kollmann Tobias R. , Way Sing Sing , Harowicz Heidi L. , Hajjar Adeline M. , Wilson Christopher B.
Published: March 2004

Neonates respond suboptimally to many vaccines. The reasons for this defect are unclear, but suboptimal antigen presentation by dendritic cells has been suggested as one possibility. In this report we describe an in vitro system that allows the generation of large numbers of resting murine neonatal dendritic cells facilitating their study. Using this system, we show a clear reduction in the ability of neonatal dendritic cells to present soluble ovalbumin, while the capacity to present ovalbumin peptide is intact. This suggests a specific defect in cross-presentation of exogenous antigen via the major histocompatibility complex (MHC) class I pathway. Deficient cross-presentation may contribute to the suboptimal CD8 T-cell response to vaccines in neonates. (Blood. 2004;103:4240-4242)
Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura
Authors: Zheng X. Long , Kaufman Richard M. , Goodnough Lawrence T. , Sadler J. Evan
Published: March 2004

Therapeutic plasma exchange is an effective empiric treatment for thrombotic thrombocytopenic purpura (TTP), but how therapy affects the level of adisintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) or inhibitor has not been reported in many patients. We prospectively analyzed ADAMTS13 activity and inhibitor levels in 37 adults with TTP. ADAMTS13 level at presentation was lower than 5% in 16 of 20 patients with idiopathic TTP and in none of 17 patients with TTP associated with hematopoietic stem cell transplantation, cancer, drugs, or pregnancy (P < .00001). Seven of the 16 patients with ADAMTS13 activity lower than 5% (≈ 44%) had inhibitors. For 8 patients followed serially with ADAMTS13 activity lower than 5% but no inhibitor at presentation, plasma exchange led to complete clinical remission and a rise in ADAMTS13 level. In contrast, 4 patients with low ADAMTS13 activity but high-titer inhibitor (> 5 units/mL) had neither a rise in ADAMTS13 activity nor a reduction in the inhibitor titer: 3 had recurrent disease and 1 died. Among 17 patients with AD-AMTS13 activity at presentation higher than 25%, 10 died. Mortality rate for idiopathic TTP was 15%, whereas mortality for nonidiopathic TTP was 59% (P < .02). We conclude that assays of ADAMTS13 activity and inhibitors in addition to the clinical categories (idiopathic TTP and nonidiopathic TTP) are predictive of outcome and may be useful to tailor patient treatment.
Thymosin α 1 activates dendritic cells for antifungal Th1 resistance through Toll-like receptor signaling
Authors: Romani Luigina , Bistoni Francesco , Gaziano Roberta , Bozza Silvia , Montagnoli Claudia , Perruccio Katia , Pitzurra Lucia , Bellocchio Silvia , Velardi Andrea , Rasi Guido , di Francesco Paolo , Garaci Enrico
Published: March 2004

Dendritic cells (DCs) show a remarkable functional plasticity in the recognition of Aspergillus fumigatus and orchestrate the antifungal immune resistance in the lungs. Here, we show that thymosin α 1, a naturally occurring thymic peptide, induces functional maturation and interleukin-12 production by fungus-pulsed DCs through the p38 mitogen-activated protein kinase/nuclear factor (NF)-κB-dependent pathway. This occurs by signaling through the myeloid differentiation factor 88-dependent pathway, involving distinct Toll-like receptors. In vivo, the synthetic peptide activates T-helper (Th) cell 1-dependent antifungal immunity, accelerates myeloid cell recovery, and protects highly susceptible mice that received hematopoietic transplants from aspergillosis. By revealing the unexpected activity of an old molecule, our finding provides the rationale for its therapeutic utility and qualify the synthetic peptide as a candidate adjuvant promoting the coordinated activation of the innate and adaptive Th immunity to the fungus. (Blood. 2004;103: 4232-4239)
Quantitative genetic variation in the hematopoietic stem cell and progenitor cell compartment and in lifespan are closely linked at multiple loci in BXD recombinant inbred mice
Authors: Henckaerts Els , Langer Jessica C. , Snoeck Hans-Willem
Published: March 2004

The number of bone marrow hematopoietic stem and progenitor cells as defined by the lineage-, Sca1++, c-kit+ (LSK) phenotype and their proliferative capacity in vitro are subject to quantitative genetic variation, and several quantitative trait loci (QTL) have been identified in young mice. Because some traits affecting hematopoiesis also change with age in a mouse strain-dependent fashion, we performed quantitative trait analysis in aged BXD recombinant inbred (RI) mice for the number and frequency of LSK cells, and for their proliferative capacity in vitro. Several novel QTL were identified. The number and frequency of LSK cells in old mice correlated inversely with lifespan. Furthermore, 4 of 7 lifespan QTL overlap with QTL contributing to the number, frequency, or proliferative capacity of LSK cells in young or old mice. Taken together, these data establish a close genetic, and perhaps functional, link between genetic variation in lifespan and characteristics of stem and progenitor cells. (Blood. 2004;104:374-379)
Pulmonary function and complications following chemotherapy and stem cell support in breast cancer
Authors: Fanfulla F , Pedrazzoli P , Da Prada GA , Bruschi C , Dacosto E , Zambelli A , della Cuna GR , Rampulla C
Published: March 2004

Pulmonary complications are frequent in patients treated with high-dose chemotherapy and autologous bone marrow transplantation for breast cancer or other solid tumours. This study analyses the development of lung toxicity, changes in respiratory function and occurrence of clinical symptoms in a group of 24 patients (mean age 46+/-7 yrs) who underwent high-dose sequential chemotherapy (HDS) with autologous peripheral blood stem cell (PBSC) support for high risk breast cancer. Clinical examination, chest radiography and lung function tests were performed before the HDS and 1 and 3 months following transplantation. Only one patient developed acute interstitial pulmonary disease which resolved after prednisone therapy. No patients developed infectious complications after transplantation. Baseline respiratory function was normal for most of the parameters. Only lung diffusing capacity of the lung for carbon monoxide (TL,CO) and maximal inspiratory pressure were below the normal range. Following PBSC transplantation only one patient had an altered vital capacity while 72.3% of patients had reduced TL,CO values at 1 month and 54.5% at 3 months after transplantation. Maximal expiratory flow at 25% forced vital capacity, TL,CO and maximal expiratory pres-sure were significantly reduced after 1 month but recovered slightly by 3 months. Arterial oxygen tension between baseline and both follow-up evaluations declined significantly in patients seropositive for human cytomegalovirus. It is concluded that this high-dose sequential chemotherapy regimen is acceptably safe since no pulmonary related mortality or respiratory infectious complications were observed. The only lung function alteration induced was an isolated diffusing capacity of the lung for carbon monoxide impairment, clinically negligible and partially recovered within 3 months.
Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages
Authors: Kohri K , Tamaoki J , Kondo M , Aoshiba K , Tagaya E , Nagai A
Published: March 2004

There is evidence that macrolide antibiotics are effective in the treatment of chronic airway inflammatory diseases, probably through actions other than their antibacterial properties. In order to determine whether macrolides affect the nitric oxide-generating system in the respiratory tract, rat pulmonary alveolar macrophages (PAMs) were studied in vitro. The release of NO was assessed by direct measurement with a specific amperometric sensor for this molecule, and the expression of type II NO synthase (NOS) messenger ribonucleic acid (mRNA) was determined by Northern blotting. Incubation of PAMs with lipopolysaccharide from Escherichia coli and recombinant human interferon-gamma caused release of NO, which was accompanied by induction of type II NOS mRNA. The release of NO was reduced by coincubation of cells with the macrolides erythromycin, clarithromycin and josamycin in a concentration-dependent manner, the maximal inhibition being 73+/-10, 81+/-6 and 84+/-9%, respectively, but was not altered by amoxycillin or cefaclor. These macrolides likewise inhibited the induction of type II NOS mRNA, whereas no inhibitory effects were observed with amoxycillin or cefaclor. These results suggest that macrolide antibiotics specifically inhibit type II NO synthase gene expression and consequently reduce NO production by rat pulmonary alveolar macrophages, which might result in attenuation of airway inflammation.
Effects of aging on surfactant forms in rats
Authors: Ueda T , Cheng G , Kuroki Y , Sano H , Sugiyama K , Motojima S , Fukuda T
Published: March 2004

Surfactant present in the alveolar space exists in two major forms: functional large aggregate forms (LA) and nonfunctional small aggregate forms (SA), but there is no information about the changes of surfactant forms and the rate of conversion of LA to SA in the aged lungs. The purpose of the present study was to investigate the developmental aspects of surfactant forms in newborn, young, middle-aged and aged rats, LA and SA were recovered from alveolar lavages of rats. The rate of conversion from LA to SA was then analysed using a surface-area cycling technique. Age-related changes of saturated phosphatidylcholine (Sat-PC) and surfactant protein A (SP-A) pool sizes were also evaluated in alveolar lavages. The alveolar lavages recovered from aged rats contained a significantly higher proportion of LA than did those obtained from young or newborn rats. There was also an age-related decrease in the rate of conversion from LA to SA in vitro. The Sat-PC pool sizes in the alveolar lavages decreased with age, but the SP-A contents were similar between young and aged rats. These results suggested that decreased form conversion may contribute to maintaining functional surfactant pool sizes in the lungs of aged rats.
Skeletal muscle strength and endurance in patients with mild COPD and the effects of weight training
Authors: Clark CJ , Cochrane LM , Mackay E , Paton B
Published: March 2004

This study poses two questions: 1) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease (COPD)? and 2) what is the effect of a randomized, controlled, 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients (age 49+/-11 yrs), mean forced expiratory volume in one second (FEV1) 77+/-23% pred and 52 healthy, sedentary subjects (age 51 (10) yrs), mean FEV1 109+/-16% pred. The 43 COPD patients were randomly allocated into training (n=26) and control (n=17) groups. Isokinetic and isotonic muscle function, whole body endurance, maximal exercise capacity and lung function were measured. The COPD patients had reduced isokinetic muscle function (with the exception of sustained upper limb strength) as compared with healthy sedentary subjects. Muscle function improved after weight training in the COPD patients. Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption. A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which cannot be explained by factors such as hypoxaemia and malnutrition. Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning.
Nasal ventilation in COPD exacerbations: early and late results of a prospective, controlled study
Authors: Bardi G , Pierotello R , Desideri M , Valdisserri L , Bottai M , Palla A
Published: March 2004

Noninvasive positive pressure mechanical ventilation (NIPPV) in exacerbated chronic obstructive pulmonary disease (COPD) has been investigated early and after 1 yr of follow-up. To this end, 30 patients were enrolled in a prospective, controlled trial: 15 had early administration of NIPPV (Group A), 15 had medical therapy only (Group B); assignment was made on the basis of equipment availability only. In-hospital mortality, need for endotracheal intubation and mean length of hospitalization were lower in Group A, though the difference was not statistically significant. Arterial oxygen tension in arterial blood (Pa,O2), carbon dioxide tension in arterial blood (Pa,CO2) and HCO3- improved significantly in both groups from admission to discharge: 45.8+/-8.6 versus 64.9+/-10.0; 59.4+/-11.8 versus 48.6+/-7.3; 34.3+/-4.3 versus 30.1+/-3.4 in group A; 49.2+/-11.4 versus 60.9+/-8.2; 52.6+/-15.9 versus 44.4+/-8.7; 31.7+/-5.9 versus 28.0+/-3.6 in group B, respectively, p<0.05 for all comparisons; pH, percentage forced expiratory volume in one second (FEV1) and tidal volume (VT) improved significantly in patients of group A only: 7.36+/-0.04 versus 7.41+/-0.02; 39.8+/-13.6 versus 49.4+/-11.7; 0.71+/-0.3 versus 0.84+/-0.4, respectively, p<0.05. During follow-up, 3, 6, and 12 months survival rates were significantly higher in Group A than in Group B (p<0.02). Hospital new admissions over 1 yr were more frequent in Group B (n=6, incidence rate: 0.216%) than in Group A (n=4, incidence rate: 0.084%). Therefore, noninvasive positive pressure mechanical ventilation may be added to "conventional" medical therapy in exacerbated chronic obstructive pulmonary disease.
Peripheral airway findings in chronic obstructive pulmonary disease using an ultrathin bronchoscope
Authors: Kikawada M , Ichinose Y , Miyamoto D , Minemura K , Takasaki M , Toyama K
Published: March 2004

The authors performed bronchoscopic examination using an ultrathin bronchoscope to determine the characteristics of the peripheral airways in chronic obstructive pulmonary disease (COPD). The study population comprised 13 healthy control subjects, 10 patients with chronic bronchitis without airflow limitation, and 20 patients with COPD. The COPD patients were divided clinically into 10 with chronic bronchitis and 10 with pulmonary emphysema. The peripheral airways were examined using an ultrathin bronchoscope. In chronic bronchitis, peripheral airways of the 11th or 12th generation showed a high frequency of obstruction and mucosal changes such as granulation. In pulmonary emphysema, the peripheral airways frequently showed a net-like appearance of the bronchial epithelium and obstruction at the 11th or 12th generation. Morphological changes of the small airways in chronic obstructive pulmonary disease can be detected by an ultrathin bronchoscope, and this method is likely to be useful for investigating the small airways in vivo.
Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD
Authors: Rutgers SR , Timens W , Kaufmann HF , van der Mark TW , Koeter GH , Postma DS
Published: March 2004

It is unclear how cellular and soluble inflammatory markers in induced sputum relate to markers in lavage fluid and biopsies in chronic obstructive pulmonary disease (COPD). This was investigated and also the possible differences between subjects with COPD and healthy controls assessed. Eighteen nonatopic subjects with COPD and 11 healthy controls were studied. Sputum was induced by inhalation of hypertonic saline. The airways were lavaged, using the first 50 mL for bronchial wash (BW) and the subsequent 150 mL for bronchoalveolar lavage (BAL), and biopsies were taken from subsegmental carinae. Neutrophils were the predominant cell type in sputum in COPD (median 77.3%) but not in BW (5.5%) and BAL fluid (1.7%). Differential cell counts in sputum did not correlate with the counts in BW or BAL fluid or biopsies, whereas sputum eosinophil cationic protein (ECP) levels correlated with BW fluid ECP levels (p=0.66, p=0.007) and sputum interleukin-8 (IL-8) concentration with BAL fluid IL-8 concentration (p= 0.52, p=0.026). Subjects with COPD had a higher percentage of sputum neutrophils and eosinophils and higher concentrations of ECP and IL-8 than healthy controls. The higher percentages of eosinophils and concentrations of ECP were also seen in BW and BAL fluid. Finally, higher numbers of macrophages and eosinophils were found in biopsies. In conclusion, induced sputum is derived from a different compartment from BW and BAL fluid and biopsies. Induced sputum may be useful for studying the contribution of luminal neutrophils and eosinophils in chronic obstructive pulmonary disease.
Theophylline improves acute mountain sickness
Authors: Fischer R , Lang SM , Steiner U , Toepfer M , Hautmann H , Pongratz H , Huber RM
Published: March 2004

A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes >2,500 m. Fourteen healthy male subjects participated in a randomized single-blind placebo-controlled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if <70 kg) or a matched placebo tablet taken twice daily. The acute mountain sickness score (AMSS) was assessed three times a day, beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure. In addition, measurements of respiratory frequency, pulse rate, oxygen saturation and arterial blood gas levels were performed. Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study (mean+/-SD 1.2+/-0.9) with placebo versus 3.6+/-0.8 with theophylline; p=0.03). During the high-altitude study, subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude (0.6 versus 2.3, p=0.03). Oxygenation was improved in both parts of the study. In conclusion, oral slow-release theophylline improves acute mountain sickness.
Clinically "small" effects of air pollution on FVC have a large public health impact. Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) - team
Authors: Kunzli N , Ackermann-Liebrich U , Brandli O , Tschopp JM , Schindler C , Leuenberger P
Published: March 2004

Epidemiological studies have repeatedly established adverse health effects due to long-term exposure to ambient air pollution. The Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) published a -3.14% decrease in forced vital capacity (FVC) per 10 microg x m(-3) increment in particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)). Compared to the within-subject variability of FVC, the effect may be considered small. This individual (or clinical) perspective is, however, misleading. The purpose of this study was to demonstrate the public health relevance of apparently "small" effects, using the impact of PM10 on FVC as an example. The scenario compares a population A, exposed to an annual mean PM10 of 20 microg x m(-3), with a population B exposed to 30 microg x m(-3) mean PM10. A shift of -3.14% in the population distribution of FVC increases the number of subjects in the lower tail of the distribution. In population B a relative increase was expected of 47% (16-91%) in the prevalence of "FVC <80% predicted", (i.e., from 5.17 to 7.59% and 5.88 to 8.65% among males and females, respectively). The relative increase in the prevalence of "FVC <70% predicted" (approximately 1% of population) was 63% (30-98%, males) and 57% (21-86%, females). An epidemiological estimate of a change in the mean value of the population distribution should not be misinterpreted as an effect on the individual level. However, the impact of a 10 microg x m(-3) increase in particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) on the number of subjects with a clinically relevant reduction in lung function is quantitatively important.
Fractional analysis of bronchoalveolar lavage fluid cytology in cystic fibrosis patients with normal lung function. Bronchoalveolar lavage for the evaluation of anti-inflammatory treatment (BEAT) study group
Authors: Ratjen F , Rietschel E , Griese M , Ballmann M , Kleinau I , Doring G , Reinhardt D , Paul K
Published: March 2004

Cystic fibrosis (CF) is associated with a neutrophil dominated airway inflammation. So far bronchoalveolar lavage (BAL) studies in CF have used pooled BAL samples which may be more representative of the alveolar compartment rather than the airways. To assess whether the first sample of a BAL is more sensitive in the evaluation of airway inflammation, the authors have studied 105 stable CF patients aged 5-37 yrs with a mean forced expiratory volume in one second (FEV1) of 96+/-15% (mean+/-SD). BAL cytology of the first and pooled samples were compared to reference values obtained in children without respiratory disease. Absolute cell counts and the percentage of neutrophils were significantly increased in CF patients. If the 95% confidence interval was used as a cut-off point, 17/105 CF patients had a normal percentage of neutrophils in pooled BAL samples, but only three also had a normal percentage of neutrophils in the first BAL aliquot. Therefore, neutrophil dominated airway inflammation is more pronounced in the first, mainly bronchial, bronchoalveolar lavage sample suggesting that sequential analysis of bronchoalveolar lavage fluid may have a higher sensitivity to detect early inflammatory changes in CF patients.
Diagnostic utility of eosinophils in the pleural fluid
Authors: Martinez-Garcia MA , Cases-Viedma E , Cordero-Rodriguez PJ , Hidalgo-Ramirez M , Perpina-Tordera M , Sanchis-Moret F , Sanchis-Aldas JL
Published: March 2004

This study was conducted to assess the prevalence of eosinophilia in 358 consecutive samples of pleural fluid (all cases corresponded to first thoracentesis), to review the cause of eosinophilic pleural effusions, and to determine whether the presence of eosinophils increases the likelihood of nonmalignant underlying disorders. Eosinophilic pleural effusions were identified in 45 patients (12.6%): malignant underlying conditions were diagnosed in 11 patients (24.4% with eosinophilic effusions) and benign aetiologies were found in 27 patients. Benign aetiologies included uncomplicated paraneumonic effusion in 10 patients, tuberculosis in seven, complicated paraneumonic in five, liver cirrhosis in three, hydronephrosis in one and pulmonary thromboembolism in one. Seven pleural effusions were idiopathic. There was no difference in the prevalence between eosinophilic and noneosinophilic effusions according to the different diagnoses. With parameters of sensitivity, specificity, pretest and post-test probability and positive and negative predictive values for any prevalence figure using the Bayes' theorem and for any value of eosinophils (both in percentage or absolute numbers) in the pleural fluid (receiver operating characteristic curve) an adequate predictor of benign disease was not found. It is concluded that pleural eosinophilia at the initial thoracentesis cannot be considered as a predictor of an underlying benign disorder.
The measurement of exhaled carbon monoxide is influenced by airflow obstruction
Authors: Togores B , Bosch M , Agusti AG
Published: March 2004

The concentration of carboxyhaemoglobin (COHb) is often estimated from measurements of carbon monoxide in the exhaled air (COexh). This study investigates whether the presence of airflow obstruction significantly alters the relationship between COexh and COHb. Eighty-one regular smokers were prospectively studied and divided in four groups according to the presence and severity of airflow obstruction (none, mild, moderate, severe). In each subject, the authors measured in this order: 1) arterial blood gases; 2) haemoglobin concentration and COHb (by co-oxymetry); 3) COexh; 4) lung volumes; and 5) forced spirometry. The size of the measurement error (deltaCO) was calculated from the difference between COHb and COexh. Neither the smoking history nor COexh were different in the four groups of subjects studied. In contrast, deltaCO increased in parallel to the degree of airflow obstruction. DeltaCO was >2% (a threshold value normally used in the clinic to separate smokers from nonsmokers) only in patients with severe airflow obstruction. A stepwise multivariate analysis showed that both forced expiratory volume in one second (FEV1) (percentage reference) and COHb contributed significantly (p<0.0001) to predict deltaCO. This study shows that the estimation of carboxyhaemoglobin from exhaled carbon monoxide measurements can be inaccurate in patients with severe airflow obstruction. In these patients, the direct measurement of carboxyhaemoglobin seems advisable in clinical practice.
Comparison of two standardized methods of methacholine inhalation challenge in young adults
Authors: Siersted HC , Walker CM , O'Shaughnessy AD , Willan AR , Wiecek EM , Sears MR
Published: March 2004

In the European Community Respiratory Health Study (ECRHS), airway responsiveness to methacholine was determined using the Mefar dosimeter protocol. Elsewhere, the 2-min tidal breathing method has become the preferred standardized method. The relationship between measurements of responsiveness by these two methods is not well established. This study measured airway responsiveness to methacholine by dosimeter and tidal breathing methods in 47 healthy asthmatic subjects aged 20-44 yrs. Tests were performed within 1 week and in random order. Baseline forced expiratory volume in one second (FEV1) varied by <10% between tests in 42/47 subjects. There was a close association between responsiveness determined by the two methods. A provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) value of < or =8.0 mg x mL(-1) (tidal method) used to categorize airway hyperresponsiveness agreed most closely with a provocative dose of methacholine causing a 20% fall in FEV1 (PD20) value of < or =0.5 mg (dosimeter method) (kappa statistic 0.78). Each doubling or halving of PC20 to define a level of hyperresponsiveness agreed closely with a doubling or halving of PD20. Assessment of airway responsiveness as provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second by the Mefar dosimeter protocol gave a close and predictable relationship with provocative concentration of methacholine causing a 20% fall in expiratory volume in one second assessed using the tidal breathing method. Airway hyperresponsiveness as determined by the accepted criterion of provocative concentration of methacholine causing a 20% fall in expiratory volume in one second < or =8 mg x mL(-1) was best correlated with provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second <0.5 mg by Mefar dosimeter.
Physiotherapy for airway clearance in paediatrics
Authors: Oberwaldner B
Published: March 2004

The basic therapeutic principles in paediatric chest physiotherapy (CPT) are identical to those applied in adults. However, the child's growth and development results in continuing changes in respiratory structure and function, and the requirement for different applications of CPT in each age group. Forced expiratory manoeuvres and coughing serve as basic mechanisms for mobilization and transport of secretions, but the reduced bronchial stability after birth requires special techniques in very young patients. High externally applied transthoracic pressures have to be avoided in order to prevent interruption of airflow. In addition, airway patency is maintained by the application of back pressure and by liberal use of continuous positive airway pressure. Since sympathomimetic bronchodilators might further decrease bronchial stability, their use must be individualized in newborns and young infants. Inspiration is a basic mechanism for inflating alveolar space behind obstructing mucus plugs. Due to a highly unstable chest, the premature baby, newborn and infant cannot distend their lung parenchyma to the same extent as can older patients. Consequently all chest physiotherapy strategies applied in this age group have to incorporate appropriate techniques for raising lung volume. Positioning serves to redistribute ventilation, but the young infant's response to gravitational forces differs substantially from that of the adult, and consequently strategies used in older patients have to be modified. In addition, the therapist has to consider pathology such as bronchial instability lesions and airway hyperresponsiveness and has to adjust the therapeutic response accordingly. It is particularly important to consider the special vulnerability of newborns and young infants and to modify therapeutic interventions to avoid the harm that could otherwise be inflicted. Consideration of these differences between infant, child and adult and careful analysis of the available mucus clearance techniques allows tailoring of an individualized therapeutic approach to the paediatric patient.
Eosinophilic pneumonia and respiratory failure associated with venlafaxine treatment
Authors: Fleisch MC , Blauer F , Gubler JG , Kuhn M , Scherer TA
Published: March 2004

Drugs are well known causes of eosinophilic lung disease. In many patients, symptoms increase slowly, pulmonary infiltrates and eosinophilia progress over weeks, and resolve upon withdrawal of the offending agent. Rarely, the disease presents like acute eosinophilic pneumonia with acute onset of symptoms and rapidly progressing infiltrates which may be associated with respiratory failure. This report describe a case of venlafaxine-induced acute eosinophilic pneumonia causing respiratory insufficiency that rapidly resolved upon institution of corticosteroid treatment. This 5-hydroxytryptamine and noradrenaline reuptake inhibitor was previously not known to cause lung or peripheral blood eosinophilia. Considering the increasing use of this class of medication physicians have to be aware of this life-threatening and fully reversible complication.
Cognate MHC–TCR interaction leads to apoptosis of antigen-presenting cells
Authors: Setterblad Niclas , Blancheteau Vincent , Delaguillaumie Alix , Michel Frédérique , Bécart Stéphane , Lombardi Giovanna , Acuto Oreste , Charron Dominique , Mooney Nuala
Published: March 2004

Antigen presentation to T lymphocytes has been characterized extensively in terms of T lymphocyte activation and eventual cell death. In contrast, little is known about the consequences of antigen presentation for the antigen-presenting cell (APC). We have determined the outcome of major histocompatibility complex class II-restricted peptide presentation to a specific T cell. We demonstrate that specific T lymphocyte interaction with peptide-presenting APCs led to apoptosis in the APC population. In contrast, T lymphocyte interaction with nonpeptide-loaded APCs or APCs loaded with monosubstituted peptide failed to induce T lymphocyte secretion of interleukin-2 and APC apoptosis. Phosphatidylserine externalization and mitochondrial depolarization were used to evaluate APC apoptosis. Fas/Fas ligand interactions were not required, but cytoskeletal integrity and caspase activation were essential for APC apoptosis. Antigen presentation leading to T lymphocyte activation is therefore coordinated with apoptosis in the APC population and could provide a mechanism of immune response regulation by eliminating APCs, which have fulfilled their role as specific ligands for T lymphocyte activation. This pathway may have particular importance for APCs, which are not sensitive to death receptor-induced apoptosis.