bluuebunny/crossref_metadata_2025 huggingface dataset:
What is a Man?
Authors: Garlick Steve
Published: October 2003

The author argues that research into men and masculinities has failed to seriously engage with some central insights of queer theory. In particular, an interrogation of how the institution of heterosexuality underlies modern constructs of masculinity has been largely untouched. Although queer theory owes much to postwar French philosophy, the author draws here on its earlier German heritage, especially Heidegger's understanding of “technology,” to consider the historical production of the idea of a “male sex” and problematize its position as a secure foundation for theorizing about “masculinity.” The eighteenth century was a key period for the emergence of the modern gender regime, and the author suggests that changes during this period, particularly in terms of secularization and men's relationship to their mortality, were central in constructing a conception of masculinity that relies on heterosexuality. Finally, the author argues, against some recent commentators, that the historical reality of masculinity must be recognized and foregrounded in attempts to overcome gendered inequalities.
Long-Term Care and Before: Current and Prospective Roles for Health Educators Working with Older People
Authors: Hosay Cynthia K.
Published: October 2003

As the number of people who are living long enough to grow old—and then living longer in old age—grows, there has been increasing attention on the roles of physicians, nurses, social workers, and health care administrators in working with older people. It is surprising, however, that little attention has been paid to the unique role health educators can play in working with older people. This article will focus on the needs of people as they age and how health educators can apply their training and skills to assist older people live fuller, healthier lives. Existing and potential roles for health educators are identified. Discussion of possible reasons for the relative dearth of health educators working with the elders is included.
The Program Plan Index: An Evaluation Tool for Assessing the Quality of Adolescent Pregnancy Prevention Program Plans
Authors: Parra-Medina Deborah , Taylor Doug , Valois Robert F. , Rousseau Michelle , Vincent Murray L. , Reininger Belinda M.
Published: October 2003

To assess process, impacts, and outcomes among 45 distinct county teen pregnancy prevention initiatives, several standardized data collection procedures, instruments, and protocols were developed including the Program Plan Index (PPI). The PPI was developed to determine if program plans met legislative requirements and were consistent with best practices in public health program planning and teen pregnancy prevention. Analysis of proposals from 45 counties revealed that 12 county plans were evaluated as deficient, 14 as low, 14 as acceptable, 4 as good, and 1 as excellent. Explanations for overall performance included the following: criteria used to develop the PPI based on an in-depth understanding of best practices, variations in the criteria for county request for proposals, lack of prevention expertise at the local level, and minimal time for grantees to draw down funds. Statewide efforts to improve funded community-based teen pregnancy prevention planning, implementation, and empowerment evaluation efforts are ongoing.
“We Are All Public Health”: September 11 and its Aftermath Through the Eyes of Public Health Educators at Ground Zero
Authors: Azar Carol F. , Ruiz Yumary
Published: October 2003

No one could have predicted the events of September 11. The days following this tragic event put public health educators' skills to the test as they transferred theory to practice to assist rescue workers, victims, and community residents to cope and rebuild their lives. As health educators working in New York City at that time, the authors were quickly thrust into experiences, roles, and responsibilities for which they thought they had little preparation. But as they worked at Ground Zero in the days immediately after the attack and later in the neighborhoods of lower Manhattan, they realized their health promotion practice and research training provided them with what they needed to play their part. This article briefly illustrates their experiences and describes the skills and knowledge they tapped into to assist the community.
The uses andabuses of science fiction
Authors: Steinmuller Karlheinz
Published: September 2003

Science fiction is one of the most successful and perhaps most influential contemporary literary genres, and surely also one of the most significant cultural factors shaping ourimages of science, technology, and - last but not least - the future. As an integral part of postmodernculture, science fiction has penetrated all fields of the media landscape: fiction, comic books, movies, even plays and musicals. Science fiction themes and images surface sometimes quite unexpectedly in everyday life, in TV commercials and video clips, not to speak of computer games. Internet enthusiasts use science fiction jargon and imagery to depict their visions of cyberspace. A generation ago, the race to the moon was at least partly inspired by the dreams of early science fiction writers and readers. For the public, technology is science fiction come true. For many scientists and engineers too, science fiction provides the imagery of their visions.
Natural writing: the case of Serres
Authors: Brown Steven D.
Published: September 2003

The immense powers to intervene in the very constitution of ‘life itself’ that have been developed by the modern life sciences pose serious questions for the basis of politics, and for common reason. In this context the life sciences may formally be seen as the principle source of instruction for rationality. The work of Michel Serres – philosopher and historian of science – provides a very different account of wisdom. Serres redistributes reason by exploring complex connections between the natural and social sciences and the humanities. His early analysis of the links or ‘translations’ between the art of Turner and the thermodynamic principles of Carnot reveals the existence of highly mediated relationships between different forms of knowledge. Although in recent years Serres has offered a revised reading of the case of Turner, exploring such links makes visible the fundamental interdependence of human affairs with a ‘socialised’ natural world in which ‘it no longer depends on us that everything depends on us’. Serres describes the foundations of a ‘new wisdom’ that is adequate to such a world, leading to a notion of the ‘third instructed’ as whoever is receptive to communication along the borderlines of disciplines.
On creating an anthology of nineteenth century literature and science
Authors: Otis Laura
Published: September 2003

This paper describes how I anthologised the ‘and’ of nineteenth century literature and science for a volume in Oxford University Press's World's Classics series. The challenge was to choose and align a hundred excerpts from novels, scientific essays, poems, and textbooks to reveal the ‘feedback loop’ of influence between literary and scientific writers. Some of the best evidence for cross-pollination I discovered in journal volumes. In repeated cycles of comments from my editor and reader, and with frequent input from friends, I found myself rethinking what it means to exchange ideas, and did my best to illustrate these interactions for general readers.
Epistemology andthe metaphor of the book
Authors: Forrai Gabor
Published: September 2003

This paper explores how metaphors drawing on the written forms of science have guided epistemological reflection. After a brief description of how cognitive metaphors work and why the written forms of science serve as natural sources of metaphor, it traces the influence of the most important of these metaphors, the metaphor of the book. I argue that this metaphor is at least partially responsible forthe following assumptions andemphases in epistemology: (1) that justification has a linear structure, (2) that mistakes should rather be prevented than corrected, (3) that pluralism does not have an important role, and (4) that theories as abstract structures are readily available. The final part of the paper contains some suggestions as to how the metaphor of the hypertext may help us to a useful perspective on the issues of coherence, discovery, and the search for information.
Immunomodulatory drug costimulates T cells via the B7-CD28 pathway
Authors: LeBlanc Richard , Hideshima Teru , Catley Laurence P. , Shringarpure Reshma , Burger Renate , Mitsiades Nicholas , Mitsiades Constantine , Cheema Puneet , Chauhan Dharminder , Richardson Paul G. , Anderson Kenneth C. , Munshi Nikhil C.
Published: September 2003

Although thalidomide (Thal) does not directly induce T-cell activation, it increases proliferation of T cells following CD3 activation. In this study, we examined the immunomodulatory effects of a more potent analog of Thal, immunomodulatory drug (IMiD), on T cells. Although IMiD3 does not directly stimulate proliferation of normal donor CD3+ T cells, it significantly costimulates proliferation of CD3+ T cells induced by CD3 ligation (stimulation index [SI], 2.4), immature dendritic cells (DCs; SI, 2.1), and mature DCs (SI, 2.6). T-cell proliferation triggered by DCs was abrogated by cytotoxic T lymphocyte antigen 4–immunoglobulin (CTLA-4–Ig), and IMiD3 partially overcomes this inhibitory effect. IMiD3 also overcomes the inhibitory effects of CTLA-4–Ig on Epstein-Barr virus (EBV) and influenza (Flu)–specific CD4 and CD8 T-cell responses, as measured by cytokine capture and enzyme-linked immunosorbent spot (ELISPOT) assay. IMiD3 did not induce up-regulation of CD28 expression on T cells, or of CD80-CD86 expression on dendritic cells. Importantly, IMiD3 triggers tyrosine phosphorylation of CD28 on T cells, followed by activation of nuclear factor κB (NF-κB), a known downstream target of CD28 signaling. These results therefore define the costimulatory mechanism whereby IMiD3 induces T-cell activation and provide the cellular and molecular basis for use of IMiD3 as an adjuvant in immunotherapeutic treatment strategies for multiple myeloma.
Therapeutic activation of Vα24+Vβ11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity
Authors: Nieda Mie , Okai Miki , Tazbirkova Andrea , Lin Henry , Yamaura Ayako , Ide Kazuki , Abraham Rick , Juji Takeo , Macfarlane David J. , Nicol Andrew J.
Published: September 2003

Human Vα24+Vβ11+ natural killer T (NKT) cells are a distinct CD1d-restricted lymphoid subset specifically and potently activated by α-galactosylceramide (α-GalCer) (KRN7000) presented by CD1d on antigen-presenting cells. Preclinical models show that activation of Vα24+Vβ11+ NKT cells induces effective antitumor immune responses and potentially important secondary immune effects, including activation of conventional T cells and NK cells. We describe the first clinical trial of cancer immune therapy with α-GalCer–pulsed CD1d-expressing dendritic cells. The results show that this therapy has substantial, rapid, and highly reproducible specific effects on Vα24+Vβ11+ NKT cells and provide the first human in vivo evidence that Vα24+Vβ11+ NKT cell stimulation leads to activation of both innate and acquired immunity, resulting in modulation of NK, T-, and B-cell numbers and increased serum interferon-γ. We present the first clinical evidence that Vα24+Vβ11+ NKT cell memory produces faster, more vigorous secondary immune responses by innate and acquired immunity upon restimulation.
Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13
Authors: Pimanda John E. , Maekawa Akiko , Wind Troels , Paxton Julian , Chesterman Colin N. , Hogg Philip J.
Published: September 2003

Severe deficiency of the von Willebrand Factor (VWF)–cleaving proteinase, ADAMTS13, is associated with the development of thrombotic thrombocytopenic purpura (TTP). Several mutations spread across the ADAMTS13 gene have been identified in association with a deficiency of VWF-cleaving proteinase activity in patients with congenital TTP. The spread of these dysfunctional mutations and the domain structure of ADAMTS13 are suggestive of a complex interaction between the enzyme and its substrate. We have studied a patient with congenital TTP who is a compound heterozygote for the Thr196Ile mutation in the metalloproteinase domain and a frameshift mutation (4143-4144insA) in the second CUB domain that results in loss of the last 49 amino acids of the protein. The VWF-cleaving proteinase activity of the truncated enzyme was comparable to that of the wild-type enzyme but its secretion from transfected COS-7 cells was about 14% of the wild type.
Intravenously applied IgG stimulates complement attenuation in a complement-dependent autoimmune disease at the amplifying C3 convertase level
Authors: Lutz Hans U. , Stammler Pia , Bianchi Valentina , Trüeb Ralph M. , Hunziker Thomas , Burger Reinhard , Jelezarova Emiliana , Späth Peter J.
Published: September 2003

Intravenously applied normal human immunoglobulin G (IgG) has anti-inflammatory effects in the treatment of autoimmune diseases. Systemic inflammation can originate from an overreacting amplification loop of the complement system. In blood, C3b2-containing complexes maintain complement amplification much better than the extremely short-lived C3b. Therefore, in patients with the complement-dependent autoimmune disease, dermatomyositis, we studied whether intravenously applied normal human IgG (IVIG) stimulated in vivo inactivation of these complexes. In the course of IVIG treatment, clinically effective in 6 of 8 patients, the concentration of C3b2-containing complexes dropped to 37% ± 14% (n = 6) of the pretreatment level when having infused 0.5 g IgG/kg body weight, increased marginally and in parallel to factor Bb thereafter until full-dose IgG was infused. By day 14 following infusion of 2 g IgG/kg body weight the concentration of C3b2-containing complexes was 66% ± 19%. The plasma concentration of C3 remained constant in myopathic or increased by 15% to 20% in amyopathic patients. In contrast to this, IVIG infusion was associated with consumption of up to 40% of plasma C4 at day 1 to 2 after completion of IVIG infusion. Thus, IVIG had an immediate and long-lasting attenuating effect on complement amplification in vivo, despite the fact that it induced classical complement pathway activation.
Allergen exposure–induced differences in CD34+ cell phenotype: relationship to eosinophilopoietic responses in different compartments
Authors: Sergejeva Svetlana , Johansson Anna-Karin , Malmhäll Carina , Lötvall Jan
Published: September 2003

We hypothesized that the allergen-induced increased number of airway eosinophils results from increased recruitment of eosinophils from bone marrow (BM) and local development of CD34+ cells into eosinophils. We also assumed that the phenotype of airway eosinophils depends on whether these cells have differentiated within BM or airway. C57BL/6 mice were sensitized and subsequently exposed to ovalbumin (OVA) on 5 consecutive days. Newly produced cells were labeled with a thymidine analog. Clonogenic activity and interleukin 5 (IL-5) release from bronchoalveolar lavage fluid (BALf) CD34+ cells were evaluated by using cell-culture techniques. Allergen exposure induces increase in CD135+ primitive myeloid progenitors within the BM CD34+ cell population, without significant changes in total number of CD34+ cells or newly produced CD34+ cells. CD34+/IL-5Rα+ cells in the first stage of cell differentiation were found only in BM, arguing that early commitment of CD34+ cells into the eosinophil lineage is restricted to the BM compartment. Allergen exposure induces a shift in differentiation of BM, blood, and BALf eosinophillineage–committed CD34+ cells toward mature eosinophils and recruitment of these cells via blood into airway. We further demonstrate in vitro that ability to multiply persists in BALf CD34+ cells but not CD34– cells, likely via autocrine IL-5 release and IL-5–induced up-regulation of IL-5Rα.
In vitro and in vivo effects of tPA and PAI-1 on blood vessel tone
Authors: Nassar Taher , Akkawi Sa'ed , Shina Ahuva , Haj-Yehia Abdullah , Bdeir Khalil , Tarshis Mark , Heyman Samuel N. , Higazi Abd Al-Roof
Published: September 2003

Tissue type plasminogen activator (tPA) is a key enzyme in the fibrinolytic cascade. In this paper we report that tPA contains 2 independent epitopes that exert opposite effects on blood vessel tone. Low concentrations of tPA (1 nM) inhibit the phenylephrine (PE)–induced contraction of isolated aorta rings. In contrast, higher concentrations (20 nM) stimulate the contractile effect of PE. The 2 putative vasoactive epitopes of tPA are regulated by the plasminogen activator inhibitor-1 (PAI-1) and by a PAI-1–derived hexapeptide that binds tPA. TNK-tPA, a tPA variant in which the PAI-1 docking site has been mutated, stimulates PE-induced vasoconstriction at all concentrations used. The stimulatory, but not the inhibitory, effect of tPA on the contraction of isolated aorta rings was abolished by anti–low-density lipoprotein receptor–related protein/α2-macroglobulin receptor (LRP) antibodies. Administering tPA or TNK-tPA to rats regulates blood pressure and cerebral vascular resistance in a dose-dependent mode. In other in vivo experiments we found that the vasopressor effect of PE is more pronounced in tPA knockout than in wild-type mice. Our findings draw attention to a novel role of tPA and PAI-1 in the regulation of blood vessel tone that may affect the course of ischemic diseases.
Long-term expansion of transplantable human fetal liver hematopoietic stem cells
Authors: Rollini Pierre , Kaiser Stefan , Faes-van't Hull Eveline , Kapp Ursula , Leyvraz Serge
Published: September 2003

Hematopoietic stem cells (HSCs), with their dual ability for self-renewal and multilineage differentiation, constitute an essential component of hematopoietic transplantations. Human fetal liver (FL) represents a promising alternative HSC source, and we previously reported simple culture conditions allowing long-term expansion of FL hematopoietic progenitors. In the present study, we used the nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse xenotransplantation assay to confirm that human FL is rich in NOD/SCID-repopulating cells (SRCs) and to show that these culture conditions repeatedly maintained short- and long-term SRCs from various FL samples for at least 28 days. Quantitative limited dilution analysis in NOD/SCID mice demonstrated for the first time that a 10- to over a 100-fold net expansion of FL SRCs could be achieved after 28 days of culture. The efficiency of this culture system may lead to an increase in the use of FL as a source of HSCs for transplantation in adult patients, as previously demonstrated with umbilical cord blood under different culture conditions. (Blood. 2004;103:1166-1170)
Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival
Authors: Novak Anne J. , Darce Jaime R. , Arendt Bonnie K. , Harder Brandon , Henderson Kathy , Kindsvogel Wayne , Gross Jane A. , Greipp Philip R. , Jelinek Diane F.
Published: September 2003

Multiple myeloma (MM) is a progressive disease that is thought to result from multiple genetic insults to the precursor plasma cell that ultimately affords the tumor cell with proliferative potential despite its differentiated phenotype and resistance to undergoing apoptosis. Altered expression of antiapoptotic factors as well as growth factors have been described in a significant number of patients. However, the key regulatory elements that control myeloma development and progression remain largely undefined. Because of the knowledge that B-lymphocyte stimulator (BLyS), a tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B-cell development and homeostasis, promotes the survival of malignant B cells, we began a coordinated study of BLyS and its receptors in MM. All MM cells studied expressed one or more of 3 known receptors (B-cell maturation antigen [BCMA], transmembrane activator and CAML interactor [TACI], and B-cell activating factor receptor [BAFF-R]) for BLyS; however, the pattern of expression was variable. Additionally, we provide evidence that BLyS can modulate the proliferative capacity and survival of MM cells. Finally, we provide evidence that BLyS is expressed by MM cells and is present in the bone marrow of patients with MM. Expression of BCMA, TACI, and BAFF-R by MM taken together with the ability of BLyS to support MM cell growth and survival has exciting implications because they may be potential therapeutic targets.
Receptor activation and 2 distinct COOH-terminal motifs control G-CSF receptor distribution and internalization kinetics
Authors: Aarts Lambertus H. J. , Roovers Onno , Ward Alister C. , Touw Ivo P.
Published: September 2003

We have studied the intracellular distribution and internalization kinetics of the granulocyte colony-stimulating factor receptor (G-CSF-R) in living cells using fusion constructs of wild-type or mutant G-CSF-R and enhanced green fluorescent protein (EGFP). Under steady-state conditions the G-CSF-R localized predominantly to the Golgi apparatus, late endosomes, and lysosomes, with only low expression on the plasma membrane, resulting from spontaneous internalization. Internalization of the G-CSF-R was significantly accelerated by addition of G-CSF. This ligand-induced switch from slow to rapid internalization required the presence of G-CSF-R residue Trp650, previously shown to be essential for its signaling ability. Both spontaneous and ligand-induced internalization depended on 2 distinct amino acid stretches in the G-CSF-R COOH-terminus: 749-755, containing a dileucine internalization motif, and 756-769. Mutation of Ser749 at position –4 of the dileucine motif to Ala significantly reduced the rate of ligand-induced internalization. In contrast, mutation of Ser749 did not affect spontaneous G-CSF-R internalization, suggesting the involvement of a serine-threonine kinase specifically in ligand-accelerated internalization of the G-CSF-R. COOH-terminal truncation mutants of G-CSF-R, found in severe congenital neutropenia, lack the internalization motifs and were completely defective in both spontaneous and ligand-induced internalization. As a result, these mutants showed constitutively high cell-surface expression.
A potential therapeutic role for small nonpeptidyl compounds that mimic human granulocyte colony-stimulating factor
Authors: Kusano Kouji , Ebara Shinji , Tachibana Koichi , Nishimura Tadahiro , Sato Susumu , Kuwaki Tomoaki , Taniyama Tadayoshi
Published: September 2003

Granulocyte colony-stimulating factor (G-CSF) stimulates the proliferation of bone marrow granulocytic progenitor cells and promotes their differentiation into granulocytes. G-CSF is therefore an important component of immune defense against pathogenic microorganisms: recombinant human G-CSF (rhG-CSF) is used to treat patients with a variety of neutropenias. In the present study, we screened approximately 10 000 small nonpeptidyl compounds and found 3 small compounds that mimic G-CSF in several in vitro and in vivo assays. These compounds induced G-CSF–dependent proliferation, but had no effect on interleukin-3–dependent, interleukin-2–dependent, interleukin-10–dependent, thrombopoietin (TPO)–dependent, or erythropoietin (EPO)–dependent proliferation. Each compound induced the phosphorylation of signal transducers and activators of transcription–3 (STAT3) and mitogen-activated protein kinase (MAPK) in a G-CSF–dependent cell line and in human neutrophils. In addition, these compounds induced hematopoietic colony formation from primary rat bone marrow cells in vitro. When subcutaneously injected into normal rats, they caused an increase in peripheral blood neutrophil counts. Furthermore, when they were administered to cyclophosphamide-induced neutropenic rats, blood neutrophil levels increased and remained elevated up to day 8. We therefore suggest that these small nonpeptidyl compounds mimic the activity of G-CSF and may be useful in the treatment of neutropenic patients.
Identification of antileucoprotease in remodelled human adult nasal surface epithelium
Authors: Marchand V , Tournier JM , Chevillard M , Polette M , Beorchia A , Klossek JM , Puchelle E
Published: September 2003

Antileucoprotease (ALP) is generally considered as a specific marker for glandular serous cells, and plays a major role in the defence of the respiratory tract against proteolytic damage. Nevertheless, several studies have identified ALP in bronchial and bronchiolar surface epithelial cells, and also an increased number of ALP-containing cells in bronchiolar tissue during the development of pulmonary diseases. In order to define more clearly whether the surface epithelium might be involved in the defence of the respiratory mucosa, we have investigated the expression of ALP by cells of the nasal surface epithelium. Indirect immunocytochemistry and in situ hybridization for ALP were performed on human nasal polyp sections. The height of the surface epithelium, its morphology, and the degree of local inflammation were assessed in parallel. Surface epithelium morphology was highly heterogeneous. ALP-containing cells were identified, but only in remodelled areas of the surface epithelium (foldings, basal cell and/or mucous cell hyperplasia), with no association to the degree of inflammation. These results demonstrate that the surface epithelial cells of the human adult nasal mucosa can express ALP in remodelled surface epithelium, and may be actively involved in the biochemical defence of the airways.
High-dose and low-dose systemic corticosteroids are equally efficient in acute severe asthma
Authors: Marquette CH , Stach B , Cardot E , Bervar JF , Saulnier F , Lafitte JJ , Goldstein P , Wallaert B , Tonnel AB
Published: September 2003

The optimal amount of systemic corticosteroids to be used in acute severe asthma remains an unresolved issue. In this double-blind, randomized study we compared two doses of methylprednisolone (1 vs 6 mg.kg-1 q.d.) in asthmatics presenting with an acute severe asthma attack, unresponsive to an intensive beta 2-agonist regimen administered during a run-in period. Concurrent therapy, including oxygen, inhaled and intravenous salbutamol, and aminophylline was strictly standardized. The response was assessed by serial bedside spirometry. The primary outcome measurement was forced expiratory volume in one second (FEV1) (expressed as percentage of predicted values) at 24 and 44 h. The trial was designed in order to achieve a statistical power of 90%. Twenty three patients were included in the low-dose group and 24 in the high-dose group. Both groups were comparable in terms of demographic profiles, history of asthma, and severity of the current attack. Improvement in pulmonary function was similar in both groups. At 44 h, the mean (+/- SD) FEV1 values were 53 +/- 22 and 45 +/- 14% in the low and in the high-dose group respectively (NS). We conclude that high dose systemic corticosteroids offer no further benefit over low-doses in the treatment of severe acute asthma.
Gas exchange response to intravenous aminophylline in patients with a severe exacerbation of asthma
Authors: Montserrat JM , Barbera JA , Viegas C , Roca J , Rodriguez-Roisin R
Published: September 2003

In patients with acute exacerbations of asthma, the intravenous administration of bronchodilators, such as salbutamol, entails the potential risk of worsening pulmonary gas exchange, despite an amelioration of airflow obstruction. The present study was designed to investigate the effect of intravenous aminophylline on pulmonary gas exchange in patients hospitalized with a severe exacerbation of asthma. We studied 12 patients (aged 41 +/- 13 yrs) admitted to the hospital because of an exacerbation of asthma. The study was of a randomized, double-blind, placebo-controlled design. Six patients were treated with intravenous aminophylline and six received placebo, in addition to standard treatment with inhaled salbutamol and intravenous corticosteroids. Forced spirometry, respiratory gas exchange, ventilation-perfusion relationships assessed with the multiple inert gas elimination technique, and systemic haemodynamics were measured at baseline and 60 min after treatment started. In the aminophylline-treated group, mean theophylline plasma levels increased to 15.2 +/- 3.6 micrograms.ml-1, forced expiratory volume (FEV1) increased by 17 +/- 12%, and forced vital capacity (FVC) by 16 +/- 10%. The mean changes in FEV1 and FVC in the aminophylline-treated group were significantly higher than in the placebo-treated group. Likewise, minute ventilation increased by 23 +/- 14% and arterial carbon dioxide tension (PaCO2) decreased by 0.4 +/- 0.3 kPa (3 +/- 2 mmHg) during aminophylline infusion. No significant changes in arterial oxygen tension (PaO2) or in ventilation-perfusion distributions were shown in aminophylline-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of pretreatment with inhaled methoxamine on bronchial responses to histamine in asthmatic subjects
Authors: Phan-Puibaraud TT , Regnard J , Monchi M , Dall'Ava-Santucci J , Lockhart A , Dinh-Xuan AT
Published: September 2003

The underlying mechanisms of bronchial obstruction in asthma are complex. Both bronchospasm and bronchial oedema are thought to play pivotal roles in asthma, but their respective importance in a given asthmatic individual is unknown. To address this question, we assessed the effects of pretreatment with inhaled methoxamine, a potent alpha 1-adrenoceptor agonist, on bronchial response to inhaled histamine in 10 asthmatic subjects. The study was conducted according to a double-blind, cross-over, randomized and placebo-controlled design. In each subject, dose-response curves for the effects on forced expiratory volume in one second (FEV1) of serially doubling doses of inhaled histamine were obtained on three different days, 15 min after pretreatment with either methoxamine (10 mg) or duplicated placebo. Histamine, first dose 100 micrograms (543 nmol), was delivered by a breath-activated dosimeter every 5 min. FEV1 was measured in triplicate after each dose and the largest value was retained. There was no difference in baseline and prechallenge FEV1 after placebo and methoxamine. Mean coefficient of variation of decrease in FEV1 induced by histamine on the two placebo days was 6.7 +/- 2%. On average, the bronchial responses to histamine were not modified by pretreatment with methoxamine as compared to placebo (delta FEV1 = 0.83 +/- 0.14 l on methoxamine versus 0.85 +/- 0.11 l and 0.86 +/- 0.13 l on the two placebo days).(ABSTRACT TRUNCATED AT 250 WORDS)
Nedocromil sodium reduces cigarette smoke-induced bronchoconstrictor hyperresponsiveness to substance P in the guinea-pig
Authors: Dusser DJ , Lacroix H , Desmazes-Dufeu N , Mordelet-Dambrine M , Roisman GL
Published: September 2003

Acute exposure to cigarette smoke provokes airway hyperresponsiveness to substance P and inactivates neutral endopeptidase (NEP). To determine whether nedocromil sodium can prevent cigarette smoke-induced hyperresponsiveness to substance P, we studied two groups of anaesthetized guinea-pigs. One group of guinea-pigs was pretreated with aerosolized 0.9% NaCl solution (90 breaths), the other group was pretreated with aerosolized nedocromil sodium (10(-4) M, 90 breaths). In each animal, pretreatment was followed by either exposure to the smoke of one cigarette or exposure to air. After acute exposure to cigarette smoke or to air, we measured the change in total pulmonary resistance (RL) induced by increasing concentrations of aerosolized substance P. In the absence of nedocromil sodium, the bronchoconstrictor responses to substance P were greater in cigarette smoke-exposed guinea-pigs than in air-exposed animals. Aerosolized nedocromil sodium had no effect on the response to substance P in air-exposed animals, but it reduced cigarette smoke-induced hyperresponsiveness to substance P. The preventive effect on cigarette smoke-induced hyperresponsiveness to substance P was observed at concentrations of aerosolized nedocromil sodium of 3 x 10(-5), 10(-4), and 3 x 10(-4) M. In vitro, cigarette smoke solution inhibited NEP activity from lung membrane preparations, but this inhibitory effect was not modified by nedocromil sodium (10(-4) M). We conclude that aerosolized nedocromil sodium reduces cigarette smoke-induced airway hyperresponsiveness to substance P in vivo. This action of nedocromil sodium is not due to a protective effect on cigarette smoke-induced inactivation of NEP in vitro.
Airway hyperresponsiveness in workers exposed to low levels of irritants
Authors: Kremer AM , Pal TM , Schouten JP , Rijcken B
Published: September 2003

The purpose of this study was to assess the association between occupational exposure to low levels of airway irritants, and airway responsiveness to histamine. In 688 male workers, symptom prevalence was assessed according to the British Medical Research Council (BMRC) questionnaire. All subjects performed a 30 s tidal breathing challenge test. Airway hyperresponsiveness (AHR) was defined as a 20% fall in forced expiratory volume in one second (FEV1) at < or = 32 mg.ml-1 histamine. On the basis of job titles and working department, the exposure status of all workers was characterized into seven groups: 1) reference group; 2) white collars; 3) SO2, HCl, SO4(2-); 4) polyester vapour; 5) oil mist and oil vapour; 6) polyamide and polyester vapour; and 7) multiple exposures. Using multiple logistic regression, no association was found between the exposure groups and a higher prevalence of AHR. A higher prevalence was significantly associated with a low FEV1, a history of allergy, and the presence of chronic respiratory symptoms. Subjects in the SO2 group and the oil mist group with < or = 5 exposure years had a lower prevalence of AHR, probably due to pre-employment selection procedures. There was some trend for subjects with more than 5 yrs exposure to polyester vapour and to oil mist and to oil vapour to have a higher prevalence of AHR. Analyses using the dose-response slope according to O'Connor, revealed similar results and provides no additional information. We conclude that no association could be demonstrated between low grade exposure to airway irritants and airway hyperresponsiveness, and that further research is needed to elucidate this relationship.
Elevated interleukin-2 receptor level in patients with active pulmonary tuberculosis and the changes following anti-tuberculosis chemotherapy
Authors: Chan CH , Lai CK , Leung JC , Ho AS , Lai KN
Published: September 2003

Soluble interleukin-2 receptor (sIL-2R) is a marker of T-lymphocyte activation. We have undertaken a study to examine the serum sIL-2R levels in patients with pulmonary tuberculosis (TB) and the changes following anti-TB chemotherapy. Forty four patients with pulmonary TB or tuberculous pleural effusion were recruited. Serum was collected from the patients before and at 1, 2, 4 and 6 months after initiation of anti-TB chemotherapy. Serum sIL-2R level was measured by an enzyme immunoassay. The mean sIL-2R level before treatment was 1,452 +/- 103 (SEM) U.ml-1, which was significantly higher than that of healthy control subjects (374 +/- 30 U.ml-1). There was no significant change in the sIL-2R level at 1 month, but there was a gradual reduction from the second month onwards. At the sixth month the mean sIL-2R level was 1080 +/- 81 U.ml-1, which was significantly lower than that before treatment. However, despite clinical improvement, the sIL-2R levels at the sixth month were still significantly higher than those of control subjects. We conclude that sIL-2R levels were elevated in patients with pulmonary TB and there was a gradual reduction following anti-TB chemotherapy. However, the sIL-2R levels were still higher than control subjects at completion of treatment, suggesting a delayed resolution of the inflammation in patients with pulmonary TB.
Carbon dioxide responsiveness in COPD patients with and without chronic hypercapnia
Authors: Scano G , Spinelli A , Duranti R , Gorini M , Gigliotti F , Goti P , Milic-Emili J
Published: September 2003

To ascertain whether and to what extent the reduced ventilatory response to a hypercapnic stimulus in chronic obstructive pulmonary disease (COPD) patients depends on a blunted chemoresponsiveness of central origin or to mechanical impairment, we studied two groups of COPD patients without (group A) and with (group B) chronic hypercapnia, but with similar degrees of airway obstruction and hyperinflation. The study was performed on 17 patients (9 normocapnic and 8 hypercapnic). Six age-matched normal subjects (group C) were also studied as a control. During a CO2 rebreathing test, ventilation (VE), mouth occlusion pressure (P0.1), and the electromyographic activity of diaphragm (Edi) were recorded and then plotted against end-tidal carbon dioxide tension (PCO2). Inspiratory muscle strength was significantly lower in the hypercapnic group (group B) compared to normocapnic group (A), and in these groups compared to the control group (C). Both patient groups exhibited significantly lower delta VE/delta PCO2 than the control group. In hypercapnics, delta P0.1/delta PCO2 was significantly lower than in normocapnics and control group, whilst mouth occlusion pressure as % of maximal inspiratory pressure delta P0.1 (% MIP)/delta PCO2 did not differ significantly among the three groups. delta Edi/delta PCO2 increased from C to A. At a PCO2 of 8.65 kPa, VE was similar in the normocapnic and control group, but lower in hypercapnics; Edi was similar in hypercapnic and control group; but greater in normocapnics. P0.1(% MIP) did not differ significantly among groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory system, lung, and chest wall mechanics after longitudinal laparotomy in rats
Authors: Moreira LF , Aires ST , Gobbi CF , Saldiva PH , Zin WA
Published: September 2003

It has been demonstrated that respiratory resistance and elastance increase whilst the abdomen remains open during longitudinal laparotomy. We wished to determine whether changes also occur after abdominal closure in the same animal preparation. In 10 sedated, anaesthetized paralysed, and mechanically-ventilated rats (309 +/- 33 (SD) g), resistances and elastances of the respiratory system, lung, and chest wall were measured both before longitudinal laparotomy and directly after abdominal closure. Furthermore, the resistances were also split into their initial and difference components, the former reflecting the Newtonian resistances and the latter representing the viscoelastic/inhomogeneous pressure dissipations in the system. For this purpose, the end inflation occlusion during constant inspiratory flow method was used. After laparotomy, no statistically significant changes were found in elastances and resistances of the respiratory system, lungs and chest wall (paired Student's t-test, significance level = 5%). It can be concluded that after midline xiphipubic laparotomy accompanied by bilateral ventro-dorsal infracostal incision, respiratory resistances and elastances were not different from those found in the control condition.
Respiratory muscle strength during continuous ambulatory peritoneal dialysis (CAPD)
Authors: Siafakas NM , Argyrakopoulos T , Andreopoulos K , Tsoukalas G , Tzanakis N , Bouros D
Published: September 2003

The purpose of this study was to investigate the effect of chronic renal failure (CRF) and continuous ambulatory peritoneal dialysis (CAPD) on respiratory muscle function. Global respiratory muscle strength was assessed by measuring mouth pressures during maximum static inspiration (PIMAX) near residual volume (RV) and expiration (PEMAX) near total lung capacity (TLC), in 26 patients. Maximum pressures, spirometry and lung volumes were measured before dialysis, 4 h after the administration of 2 l of dialysate into the peritoneal cavity, and just after the next drainage. In addition, biochemical indices (urea, creatinine, sodium, potassium, calcium and phosphorus) and haematological indices (haemoglobin (Hb) and haematocrit (Hct)) were measured once before the treatment. The results showed that mean PIMAX and PEMAX were normal, with a very wide range between patients, before CAPD. However, seven patients (27%) showed a PIMAX of < 75% predicted (pred) and eight (31%) a PEMAX < 75% pred. Maximal pressures decreased significantly during CAPD and increased again after the drainage of fluid. Similarly, lung volumes were within the normal range before and decreased significantly during CAPD. The forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio did not change. We conclude that respiratory muscle strength was preserved in the majority of the patients with chronic renal failure treated with CAPD. During CAPD, lung volumes and respiratory muscle function were decreased, demonstrating an effect of the abdominal cavity on the mechanics of the respiratory system. However, the decrease in the maximum pressures was less than 20%, indicating that CAPD is a safe procedure in patients without pre-existing pulmonary disease or uraemic pulmonary complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunological functions of the pulmonary epithelium
Authors: Thompson AB , Robbins RA , Romberger DJ , Sisson JH , Spurzem  , Teschler H , Rennard SI
Published: September 2003

The mature pulmonary epithelium forms a continuous lining to the airspace. Recent data suggest that this specialized epithelium may also contribute to host defence via interactions with inflammatory cells. Pulmonary epithelial cells can serve as part of the local immune system, providing structures and functions crucial for the maintenance of normal pulmonary function. This article will briefly review the morphology and development of the pulmonary epithelial cells, their function with regard to host defence, alterations of the pulmonary epithelium associated with airway diseases, and potential therapeutic implications for the treatment of respiratory diseases.
History of diaphragm physiology: the achievements of Galen
Authors: Derenne JP , Debru A , Grassino AE , Whitelaw WA
Published: September 2003

Galen (129-200 AD) produced a large written output which was to remain one of the major basis of clinical medicine for centuries. His contribution to respiration, reported in his own books and in those of Oribasius, was that of a chest physician and of an experimental physiologist. He described in minute details how to perform a remarkable series of experiments by which he demonstrated the anatomy and function of the respiratory muscles. He described the actions of the diaphragm and how it moves the rib cage, in a series of spinal chord sections and muscle denervations. He investigated the passive or active nature of expiration and made fine observations of lung movements through the exposed pleural space. He described the interaction between the lungs and chest wall and developed the concept of interaction between ribcage and abdominal muscles in maintaining the position of the diaphragm, showing a clear understanding of the principle that the diaphragm can move upward during an isovolume manoeuvre as long as the ribcage is allowed to expand. A skillful clinician, Galen applied his theories of the analysis of problems at the bedside, particularly in patients affected with dyspnoea which he attributed to respiratory muscle dysfunction.
Measurement of flow through perfused bronchial segments: optimization of flow head resistance
Authors: McFawn PK , Sparrow MP , Mitchell HW
Published: September 2003

Techniques for measuring flow, for example through perfused bronchial segments, frequently use a flow head as the sensing device. The sensitivity of these instruments to changes in airway resistance is dependent on the flow head resistance. This study aims to quantify the effect of flow head resistance on sensitivity and flow, allowing optimization of flow head resistance. A mathematical model of the perfused bronchial segment preparation was constructed and used to explore the effect of flow head resistance on sensitivity. The model's assumptions were experimentally tested using segments of pig bronchus, perfused through the lumen with Krebs solution. The model suggests a complex relationship between flow head resistance and sensitivity that has a distinct maximum when approximately half of the total resistance is present in the flow head. Furthermore, the maximum sensitivity was found to be proportional to the resting flow. Regression between experimentally derived sensitivities and modelled predictions was linear, with a correlation coefficient of 0.93. We have defined the optimum recording conditions for study of flow through isolated bronchial segments.
Pressure sensor plethysmography: a method for assessment of respiratory motion in children
Authors: Banovcin P , Seidenberg J , von der Hardt H
Published: September 2003

Noncalibrated respiratory inductance plethysmography has been used to measure respiratory function by calculation of the phase angle and, more recently, by determination of the ratio of each time to reach peak tidal expiratory flow to total expiratory time (TPEF/TE). Since TPEF/TE is known to be decreased in airway obstruction when derived from flow signals obtained by a pneumotachograph, we wanted to develop an alternative method to measure rib cage and abdominal respiratory movements. For this purpose, we used two pressure sensors attached to the skin above the umbilicus and in the right medioclavicular line at the fourth intercostal space: "pressure sensor plethysmography". We tested the ability of this method to assess thoracoabdominal asynchrony and TPEF/TE by comparison with respiratory inductance plethysmographic and pneumotachographic measurements in 30 children, aged 1-12 yrs, with airway obstruction. The mean difference (95% confidence interval (95% CI)) between phase angles obtained by respiratory inductance plethysmography and pressure sensor plethysmography was only -5.8 degrees (range -18.0 to +6.4 degrees). Similarly, all methods used to measure TPEF/TE agreed well: mean differences (95% CI) between pneumotachographic and respiratory inductance plethysmographic, pneumotachographic and pressure sensor plethysmographic, and respiratory inductance plethysmographic and pressure sensor plethysmographic measurements of TPEF/TE were +0.01 (range -0.05 to +0.06), -0.03 (-0.09 to +0.03) and -0.03 (-0.10 to +0.04), respectively. We conclude that pressure sensor plethysmography is a simple and noninvasive method, and suitable to measure thoracoabdominal asynchrony and TPEF/TE ratios as well as respiratory inductance plethysmography and pneumotachography.
Home care in cystic fibrosis patients
Authors: van Aalderen WM , Mannes GP , Bosma ES , Roorda RJ , Heymans HS
Published: September 2003

Intravenous antibiotics and enteral tube feeding at home for the treatment of pulmonary exacerbations and underweight condition in cystic fibrosis (CF) patients have become tools that are used in many cystic fibrosis centres. The experience with home care programmes from different countries is quite conclusive. If the necessary preparations are made, such as training of staff and patients, and financial support is arranged, home care is easy to put into practice. Optimal patient compliance is also necessary. Home care is as effective as hospital treatment for selected patients, and less expensive. Experience has increased during many treatment periods in different cystic fibrosis centres, and only a few adverse events have been recorded, indicating that home care is safe. However, the most important gain for cystic fibrosis patients is the reduction of hospital admission time, which means a definite improvement in the quality of life.
Lymphocytic bronchitis/bronchiolitis in a patient with primary biliary cirrhosis
Authors: Chatte G , Streichenberger N , Boillot O , Gille D , Loire R , Cordier JF
Published: September 2003

A 39 year old woman with severe primary biliary cirrhosis progressively developed exercise dyspnoea due to airflow obstruction. Sjogren's syndrome was not present. Bronchial and pulmonary biopsies demonstrated constrictive lymphocytic bronchitis/bronchiolitis, possibly a component of a generalized autoimmune process in this patient.