bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrograde Ag-enrichment in fahlores from the Coeur d'Alene mining district, Idaho, USA
Authors: Sack R. O. , Kuehner S. M. , Hardy L. S.
Published: July 2002

Tetrahedrite fahlores from the Coeur d'Alene mining district (Idaho) have been found to be enriched in Ag by the Ag–Cu exchange reaction

which occurred during cooling following galena mineralization. This solid–state reaction resulted in quantitative removal of Ag (in a AgSbS2 component) from galena and development of bournonite coronas on fahlore grains. The reaction produced a distinct population of high-Ag fahlores found in galena-rich samples and accounts for all of the bournonite mineralization. The most argentian of these high-Ag fahlores examined in this study (molar Ag/(Ag+Cu) = 0.303±0.011 and 0.336±0.011) are found in samples which achieved saturation with respect to other Ag-sulfosalts, namely pyrargyrite and polybasite and diaphorite, respectively. Multiple lines of evidence for the Ag-Cu exchange reaction are presented in this paper which applies mass-balance constraints and a thermodynamic database for sulfides/sulfosalts to microprobe analyses and textural observations, and to bulk production data. This solid-state reaction may explain why previous district studies have been unable to demonstrate convincingly primary fahlore zoning. Based on the Ag/(Ag+Cu) of fahlores coexisting with other Agsulfosalts and Fe-Zn partitioning between fahlore and sphalerite, we estimate that fahlore compositions were frozen in by 175°C. Examining the composition data for other Ag tetrahedrite fahlores found in the Coeur d'Alene district and elsewhere, we conclude that the thermodynamic database provides an accurate description of phase equilibria, except possibly for very Fe-rich systems where further studies of the Fe-Zn partitioning between fahlore and Fe-rich (Zn,Fe)S phases and of the thermodynamics of Fe-rich (Zn,Fe)S phases are warranted.
A modern, evaporitic occurrence of teruggite, Ca4MgB12As2O28.18H2O, and nobleite, CaB6O10.4H2O, from the El Tatio geothermal field, Antofagasta Province, Chile
Authors: Rodgers K. A. , Greatrex R. , Hyland M. , Simmons S. F. , Browne P. R. L.
Published: July 2002

Teruggite is the dominant phase in a soft, off-white, poorly-layered and weakly-cemented surface crust, 10–15 mm thick, occurring in the high-temperature El Tatio geothermal field of Chile. Other minerals present include halite, which is present throughout but also forms a thin (<0.5 mm), brittle, cratered surface to the deposit, nobleite, ulexite and opal-A, with possible traces of illite-smectite and at least one unidentified phase. With the exception of ulexite, none of the minerals associated with teruggite at El Tatio has been reported from other occurrences of this mineral, nor do they occur with nobleite in its sole other known occurrence in Death Valley. EDS and XPS analyses of the main mass of the deposit show the presence of Ca, As, B, Na, and Cl, consistent with the identified mineral assemblage, but with elevated concentrations in Ca and Cl that are presumably associated with a further phase. Little Mg is present and the El Tatio teruggite appears deficient in this element, with Ca presumably replacing Mg in the structure. Unlike earlier documented occurrences of teruggite, that at El Tatio is evaporitic, modern and surficial. It is located some 50 m from the nearest hot (~50°C) pool and there is no evidence of association with fluid discharge. As such, the deposit has presumably derived from a fluid moving in the uppermost levels of the El Tatio field; perhaps a heavily modified version of the brines found in the deep wells.
Cummingtonite in the Dalradian of NE Scotland
Authors: Smith C. G. , Phillips E. R.
Published: July 2002

The first recorded occurrence of cummingtonite in the Scottish Dalradian is described. The mineral occurs in thin layers within a psammite-semipelite sequence forming the lower part of the Easdale Subgroup in which it coexists with bytownitic plagioclase, almandine-rich garnet and quartz. Textural and mineral chemical evidence suggest that the cummingtonite developed from hornblende during amphibolite-facies regional metamorphism. The protolith to this cummingtonite-bearing rock is believed to have been a basaltic tuff, possibly alkaline in character, containing a significant proportion of sedimentary detritus. The cummingtonite-bearing rock may provide the earliest record of basic volcanism in the Dalradian of the Ballater district.
Chromian illite-ankerite-quartz parageneses from the Kintail district of
southern Ross-shire, Scotland
Authors: Clifford T. N. , Rex D. C. , Green R. , le Roex A. P. , Pienaar H. S. , Bühmann D.
Published: July 2002

The Coire Dhuinnid fault zone contains emerald green chromian
illite-ankerite-quartz rocks that are similar in appearance to the fuchsite(or
mariposite)-carbonate-quartz parageneses that are commonplace in Archaean
greenstone belts but which are rather rare in Phanerozoic rocks. The chromian
illite contains 2.3 wt.% Cr2O3, low
K2O (7.1–7.6 wt.%) and high H2O+ (5.7
wt.%), and it is a 1M polytype with ≤10% of an illite/smectite interstratification
indicative of a formation temperature of c. 175–200°C.
The host rocks contain high concentrations of Ni and Cr, and show low
concentrations of Ti, Nb, Y and Zr, suggesting a former primitive mafic protolith
(boninitic magma?); they are considered to be retrograde remnants of Lewisian
rocks. The latter, and the associated rocks of the Moine Series, have been
affected by CO2 metasomatism that was accompanied by the
addition of Ca(+Sr), Fe and Mg, and by the removal of Na from, and the addition of
H2O to the Moine metasediments. Radiogenic isotope studies
of mineral separates and whole rock from sample no. 43 yielded ages of 483±2 Ma
(Ar-Ar dating on Cr illite), 413±12 Ma (K-Ar dating on Cr illite), and 322±9 Ma
(Rb-Sr dating on minerals and whole rock); the significance of this discrepant
pattern is discussed.
Re-examination of yushkinite: chemical composition, optical properties and
interlayer charge transfer
Authors: Moëlo Y. , Rouer O. , Cario L. , Cervelle B.
Published: July 2002

The hydroxy-sulphide yushkinite from the type deposit has been re-examined by
electron probe microanalysis and reflectance measurement. The EPMA indicates minor
Cu (up to 1.5 wt.%) and confirms an excess of V. Taking into account its composite
structure (brucite-like hydroxide layer alternating with a berndtite-type sulphide
layer) the proposed structural formula is, with the addition of minor intercalated
Cu:
[(Mg0.71Al0.36V0.03)Σ1.10(OH)2.18O0.02]Cu0.02
[VS2]. At the crystal scale, some crystal edges give a
variable excess of Si and Al (in the 1/1 ratio), indicating a late topotactic
intergrowth with a layered alumino-silicate (or a composite silicate-sulphide).
New specular reflectance data are given in air and oil from 400 to 800 nm, with
the polarization plane parallel or perpendicular to the elongation. The refractive
index n and absorption coefficient
k are given; no absorption band exists in the
perpendicular position, with constant n close to 1.9,
and k to 0.3. In a parallel position, a
pseudo-transparency window is centred around 500–520 nm (∼2.4 eV). The main
absorption band, centred around 730 nm (∼1.7 eV), corresponds probably to a
transition t2g → eg related to
intra-layer V-V bonding. Charge transfer from the brucite-type layer to the
VS2 one, strictly controlled through H-bonding, induces a
mean formal valency of V close to 3.6. Yushkinite is compared with other synthetic
layered hydroxy-sulphides, as well as brucite-type intercalated
compounds.
Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus
Authors: Huang Christene A. , Fuchimoto Yasushi , Gleit Zachary L. , Ericsson Thomas , Griesemer Adam , Scheier-Dolberg Rachel , Melendy Elizabeth , Kitamura Hiroshi , Fishman Jay A. , Ferry Judith A. , Harris Nancy Lee , Patience Clive , Sachs David H.
Published: July 2002

Posttransplantation lymphoproliferative disease (PTLD) is a major complication of current clinical transplantation regimens. The lack of a reproducible large-animal model of PTLD has limited progress in understanding the pathogenesis of and in developing therapy for this clinically important disease. This study found a high incidence of PTLD in miniature swine undergoing allogeneic hematopoietic stem cell transplantation and characterized this disease in swine. Two days before allogeneic peripheral blood stem cell transplantation, miniature swine were conditioned with thymic irradiation and in vivo T-cell depletion. Animals received cyclosporine daily beginning 1 day before transplantation and continuing for 30 to 60 days. Flow cytometry and histologic examination were performed to determine the cell type involved in lymphoproliferation. Polymerase chain reaction was developed to detect and determine the level of porcine gammaherpesvirus in involved lymph node tissue. PTLD in swine is morphologically and histologically similar to that observed in human allograft recipients. Nine of 21 animals developed a B-cell lymphoproliferation involving peripheral blood (9 of 9), tonsils, and lymph nodes (7 of 9) from 21 to 48 days after transplantation. Six of 9 animals died of PTLD and 3 of 9 recovered after reduction of immunosuppression. A novel porcine gammaherpesvirus was identified in involved tissues. Miniature swine provide a genetically defined large-animal model of PTLD with many characteristics similar to human PTLD. The availability of this reproducible large-animal model of PTLD may facilitate the development and testing of diagnostic and therapeutic approaches for prevention or treatment of PTLD in the clinical setting.
Receptor engagement by viral interleukin-6 encoded by Kaposi sarcoma–associated herpesvirus
Authors: Aoki Yoshiyasu , Narazaki Masashi , Kishimoto Tadamitsu , Tosato Giovanna
Published: July 2002

Receptor usage by viral interleukin-6 (vIL-6), a virokine encoded by Kaposi sarcoma– associated herpesvirus, is an issue of controversy. Recently, the crystal structure of vIL-6 identified vIL-6 sites II and III as directly binding to glycoprotein (gp)130, the common signal transducer for the IL-6 family of cytokines. Site I of vIL-6, however, comprising the outward helical face of vIL-6, where human IL-6 (hIL-6) would interact with the specific α-chain IL-6 receptor (IL-6R), is accessible and not occupied by gp130. This study examined whether this unused vIL-6 surface is available for IL-6R binding. By enzyme-linked immunosorbent assay, vIL-6 bound to soluble gp130 (sgp130) but not to soluble IL-6R (sIL-6R). Using plasmon surface resonance, vIL-6 bound to sgp130 with a dissociation constant of 2.5 μM, corresponding to 1000-fold lower affinity than that of hIL-6/sIL-6R complex for gp130. sIL-6R neither bound to vIL-6 nor affected vIL-6 binding to gp130. In bioassays, vIL-6 activity was neutralized by 4 monoclonal antibodies (mAbs) recognizing a domain within vIL-6 site I, mapped to the C-terminal part of the AB-loop and the beginning of helix B. The homologous region in hIL-6 participates in site I binding to IL-6R. In addition, binding of vIL-6 to sgp130 was interfered with specifically by the 4 neutralizing anti–vIL-6 mAbs. Based on the vIL-6 crystal structure, the vIL-6 neutralizing mAbs map outside the binding interface to gp130, suggesting that they either produce allosteric changes or block necessary conformational changes in vIL-6 preceding its binding to gp130. These results document that vIL-6 does not bind IL-6R and suggest that conformational change may be critical to vIL-6 function.
Improved superoxide-generating ability by interferon γ due to splicing pattern change of transcripts in neutrophils from patients with a splice site mutation inCYBB gene
Authors: Ishibashi Fuminari , Mizukami Tomoyuki , Kanegasaki Shiro , Motoda Lena , Kakinuma Ryota , Endo Fumio , Nunoi Hiroyuki
Published: July 2002

Chronic granulomatous disease (CGD) is an inherited disorder of host defense against microbial infections caused by defective activity of the phagocyte NADPH oxidase. Based on an increase of neutrophil superoxide-generating ability in response to interferon γ (IFN-γ) in a single patient with CGD, multicentered group studies demonstrated a beneficial effect of prophylactic IFN-γ. However, no apparent increase of the phagocyte superoxide generation was found in patients enrolled in these studies. The present report offers an additional kindred in whom an IFN-γ–dependent increase in neutrophil superoxide production was observed in 3 affected patients. The defect in the CYBB gene for gp91-phox was identified as an otherwise silent mutation adjacent to the third intron of theCYBB gene that alters messenger RNA splicing. By molecular analysis, significant differences were found in the splicing pattern ofCYBB gene transcripts in patient neutrophils between 1 and 25 days after administration of IFN-γ. Furthermore, a complete transcript containing the missing exons could be detected in all specimens after the treatment. The changes in the splicing pattern of the transcripts and the prolonged effect on superoxide-generating ability of patient neutrophils indicate that IFN-γ induced a partial correction of the abnormal splicing of CYBB gene transcripts in myeloid progenitor cells.
Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients
Authors: Müller Susanna M. , Ege Markus , Pottharst Annette , Schulz Ansgar S. , Schwarz Klaus , Friedrich Wilhelm
Published: July 2002

A study in 121 infants with severe combined immunodeficiency (SCID) was performed to determine the prevalence of an engraftment by transplacentally acquired maternal T cells and to explore clinical and immunological findings related to this abnormality. Each newly diagnosed patient with SCID presenting with circulating T cells was evaluated for chimerism by performing selective HLA typing of T cells and non–T cells. In patients with engraftment, maternal T cells were characterized phenotypically and functionally, and results were correlated with clinical findings in the patients. Maternal T cells were detected in the circulation in 48 patients; these cells ranged from fewer than 100/μL in 14 cases to more than 2000/μL in 4 cases (median, 415/μL). Clinical signs of graft-versus-host disease (GVHD) were absent in 29 patients. In the other cases, manifestations of GVHD were present, involving the skin and in 14 cases also the liver. Skin GVHD was mild in 8 patients. In these patients, as well as in patients with no signs of GVHD, maternal T cells were predominantly CD8+ and, with one exception, failed to respond to mitogen stimulation. In 9 patients, manifestations of skin GVHD were prominent. T cells in these cases were predominantly CD4+ and responded, with one exception, to mitogen stimulation. In 8 of the cases with prominent skin GVHD, the underlying SCID variant was characterized by the absence of B cells. In this study, further understanding is provided of a phenomenon that is responsible for the significant heterogeneity of clinical and immunological findings in SCID.
Transduction of a dominant-negative H-Ras into human eosinophils attenuates extracellular signal–regulated kinase activation and interleukin-5–mediated cell viability
Authors: Hall David J. , Cui Jin , Bates Mary Ellen , Stout Barbara A. , Koenderman Leo , Coffer Paul J. , Bertics Paul J.
Published: July 2002

Inhibition of eosinophil apoptosis by exposure to interleukin-5 (IL-5) is associated with the development of tissue eosinophilia and may contribute to the inflammation characteristic of asthma. Analysis of the signaling events associated with this process has been hampered by the inability to efficiently manipulate eosinophils by the introduction of active or inhibitory effector molecules. Evidence is provided, using a dominant-negative N17 H-Ras protein (dn-H-Ras) and MEK inhibitor U0126, that activation of the Ras-Raf-MEK-ERK pathway plays a determining role in the prolongation of eosinophil survival by IL-5. For these studies, a small region of the human immunodeficiency virus Tat protein, a protein transduction domain known to enter mammalian cells efficiently, was fused to the N-terminus of dn-H-Ras. The Tat-dn-H-Ras protein generated from this construct transduced isolated human blood eosinophils at more than 95% efficiency. When Tat-dn-H-Ras–transduced eosinophils were treated with IL-5, they exhibited a time- and dosage-dependent reduction in extracellular regulated kinase 1 and 2 activation and an inhibition of p90 Rsk1 phosphorylation and IL-5–mediated eosinophil survival in vitro. In contrast, Tat-dn-H-Ras did not inhibit CD11b up-regulation or STAT5 tyrosine phosphorylation. These data demonstrate that Tat dominant-negative protein transduction can serve as an important and novel tool in studying primary myeloid cell signal transduction in primary leukocytes and can implicate the Ras-Raf-MEK-ERK pathway in IL-5–initiated eosinophil survival.
Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies
Authors: Sanz Guillermo F. , Saavedra Silvana , Planelles Dolores , Senent Leonor , Cervera Jose , Barragán Eva , Jiménez Carmen , Larrea Luis , Martı́n Guillermo , Martı́nez Jesús , Jarque Isidro , Moscardó Federico , Plumé Gemma , Andreu Rafael , Regadera Ana I. , Garcı́a Inmaculada , Mollá Susana , Solves Pilar , de la Rubia Javier , Bolufer Pascual , Benlloch Luis , Soler Marı́a A. , Marty Marı́a L. , Sanz Miguel A.
Published: July 2002

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 × 107/kg (range, 1.01 × 107/kg to 4.96 × 107/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 × 109/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 × 109/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P = .01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.
Oligodeoxynucleotide-mediated inhibition of c-myb gene expression in autografted bone marrow: a pilot study
Authors: Luger Selina M. , O'Brien Stephen G. , Ratajczak Janina , Ratajczak Mariusz Z. , Mick Rosemarie , Stadtmauer Edward A. , Nowell Peter C. , Goldman John M. , Gewirtz Alan M.
Published: July 2002

Antisense oligodeoxynucleotide (ODN) drugs might be more effective if their delivery was optimized and they were targeted to short-lived proteins encoded by messenger RNA (mRNA) species with equally short half-lives. To test this hypothesis, an ODN targeted to the c-mybproto-oncogene was developed and used to purge marrow autografts administered to allograft-ineligible chronic myelogenous leukemia patients. CD34+ marrow cells were purged with ODN for either 24 (n = 19) or 72 (n = 5) hours. After purging, Myb mRNA levels declined substantially in approximately 50% of patients. Analysis of bcr/abl expression in long-term culture-initiating cells suggested that purging had been accomplished at a primitive cell level in more than 50% of patients and was ODN dependent. Day-100 cytogenetics were evaluated in surviving patients who engrafted without infusion of unmanipulated “backup” marrow (n = 14). Whereas all patients were approximately 100% Philadelphia chromosome–positive (Ph+) before transplantation, 2 patients had complete cytogenetic remissions; 3 patients had fewer than 33% Ph+ metaphases; and 8 remained 100% Ph+. One patient's marrow yielded no metaphases, but fluorescent in situ hybridization evaluation approximately 18 months after transplantation revealed approximately 45% bcr/abl+ cells, suggesting that 6 of 14 patients had originally obtained a major cytogenetic response. Conclusions regarding clinical efficacy of ODN marrow purging cannot be drawn from this small pilot study. Nevertheless, these results lead to the speculation that enhanced delivery of ODN, targeted to critical proteins of short half-life, might lead to the development of more effective nucleic acid drugs and the enhanced clinical utility of these compounds in the future.
Sustained response to recombinant human erythropoietin and intermittent all-trans retinoic acid in patients with myelodysplastic syndromes
Authors: Stasi Roberto , Brunetti Maurizio , Terzoli Edmondo , Amadori Sergio
Published: July 2002

In vitro studies suggest that all-trans retinoic acid (ATRA) synergizes with erythropoietin (EPO) for the stimulation of hematopoiesis in patients with myelodysplastic syndrome (MDS). A clinical trial was performed to evaluate whether a combination of these agents was effective in relieving the cytopenias associated with MDS. Twenty-seven patients with low- or intermediate-risk MDS were enrolled in a 12-week study. ATRA was administered orally at the dose of 80 mg/m2 per day in 2 divided doses for 7 consecutive days every other week. Recombinant human EPO was given subcutaneously 3 times a week. The EPO dose was initiated at 150 U/kg and was increased to 300 U/kg if after 6 weeks there was no or there was suboptimal erythroid response. Patients who responded to therapy were continued on ATRA and EPO at the same doses for 6 additional months (extension phase). Further treatment was given to patients with a continued response. Clinically significant erythroid responses with increases of hemoglobin levels of at least 1 g/dL or reduction of transfusion needs were seen in 13 (48%) patients, with 4 showing improved responses after dose escalation of EPO. Ten (37%) patients displayed continued responses during 6 months of extended treatment, and 7 (26%) are still responsive after a follow-up period of 13 months. Neutrophil responses were observed in 5 of 12 patients with neutropenia, and platelet responses were observed in 6 of 9 patients with thrombocytopenia. Three patients displayed trilineage responses that were sustained during continuation therapy. Side effects were observed in all patients but were of mild entity and did not require discontinuation of therapy. It is concluded that the combination ATRA + EPO is an effective and well-tolerated treatment for patients with low- and intermediate-risk MDS. The optimal ATRA and EPO schedule and the role of maintenance treatment remain to be determined and warrant further investigation.
Effects of PEEP on inspiratory resistance in mechanically ventilated COPD patients
Authors: Guérin C. , Fournier G. , Milic-Emili J.
Published: July 2002

This study aimed to investigate the effect of increased lung volume with positive end-expiratory pressure (PEEP) on respiratory resistance in patients with chronic obstructive pulmonary disease (COPD).

Ten patients with COPD were mechanically ventilated for acute respiratory failure. PEEP was set at 0, 5, 10 and 15 cmH2O. Using the rapid airway occlusion technique, the total inspiratory resistance of the respiratory system was partitioned into interrupter (Rint,rs) and additional effective (ΔRrs) resistances. At each level of PEEP, at constant inflation flow, the inflation volume (ΔV) was varied from 0.2–1 L, and, at constant ΔV, the inflation flow was varied from 0.2–1.2 L·s−1. The changes in end-expiratory lung volume (ΔEELV) induced by PEEP were also measured.

The difference between the EELV and the relaxation volume of the respiratory system (ΔFRC) increased significantly with PEEP of 10 and 15 cmH2O as compared to a PEEP of 0, the increase being associated with a significant reduction ofRint,rs. By contrast, ΔRrswas independent of ΔFRC. At constant ΔV,Rint,rsfitted Rohrer's equation (Rint,rs=K1+K2×flow). While K2significantly declined with ΔFRC, K1did not change. At all levels of PEEP, ΔRrswas not influenced by ΔFRC.

With increasing lung volume induced by positive end-expiratory pressure, the inspiratory airway resistance decreased, whereas the viscoelastic behaviour of the respiratory system, as reflected by additional effective resistance, did not change.
Influence of neonatal screening and centralized treatment on long-term clinical outcome and survival of CF patients
Authors: Mérelle M.E. , Schouten J.P. , Gerritsen J. , Dankert-Roelse J.E.
Published: July 2002

After an experimental neonatal screening program for cystic fibrosis (CF) from 1973–1979, a follow-up study took place from 1980–1997. Patients were treated at specialized centres (C) or at local hospitals (non-C). Aims of the study were: 1) to determine whether the previously reported benefits from screening persisted with time and after adjustment for confounding variables; and 2) to investigate whether centre treatment was associated with improved prognosis of CF patients.

Prognosis of patients detected by screening (S; n=24) was compared with patients detected clinically, born during (non-S; n=29) and after the screening programme (post-S; n=39). In addition, prognosis was compared between 45 C and 47 non-C patients. Multivariable regression analysis was used to compare survival and mixed-effects model regression analysis was used to compare clinical outcome between patients. The analyses included the variables screening, centre treatment, sex, meconium ileus and genotype.

S patients had a significantly smaller decline in forced expiratory volume in one second (FEV1) (difference +2.74% predicted) and significantly lower immunoglobulin-G (IgG) levels (difference −473.69 mg·dL−1) than non-S patients until 12 yrs of age. At 12 yrs of age, vital capacity was significantly higher in S patients than in non-S patients (difference +362.79 mL). Survival seemed to be best for S patients compared to both non-S and post-S patients. Post-S patients were significantly heavier (difference in sd weight +0.77), had a significantly smaller decline in FEV1(difference +2.80% pred) and lower IgG levels (difference −453.04 mg·dL−1) than non-S patients until 12 yrs of age. C patients had a significantly improved survival (relative risk (RR) 0.18, 95% confidence interval 0.05–0.57) than non-C patients.

Early diagnosis through neonatal screening leads to better preservation of lung function in the long term in cystic fibrosis patients. Management of cystic fibrosis patients in specialized centres improves survival.
Determinants of cough in young adults participating in the European Community Respiratory Health Survey
Authors: Janson C. , Chinn S. , Jarvis D. , Burney P.
Published: July 2002

Cough is a common symptom that affects a large proportion of the general population. The aim of this investigation was to identify determinants of nocturnal, nonproductive and productive cough in population samples from different countries.

In a cross-sectional international population survey, 18,277 subjects (20–48 yrs) from 16 countries answered an interview-led questionnaire. Total and specific immunoglobulin-;E was measured and spirometry was performed. Three types of cough were defined: nocturnal, nonproductive and productive cough. The relation of the independent variables to cough was estimated by means of logistic regression for each centre or country and combined across centre or country by random-effects meta-analysis.

The median prevalence of nocturnal, nonproductive and productive cough in the different centres was 30.7%, 10.2% and 10.2%, respectively. Nocturnal and nonproductive cough were related to female sex (adjusted odds ratio (OR)=2.08 and 1.27, respectively), while nocturnal and productive cough were related to rhinitis (OR=1.46 and 1.61, respectively). All three types of cough were related to asthma, tobacco smoking, environmental tobacco smoke and obesity.

Females are more likely to report nocturnal and nonproductive cough than males. Cough was related to treatable disorders, like asthma and rhinitis, as well as avoidable factors, such as tobacco smoking and environmental tobacco smoke.
Development and validation of the Adolescent Asthma Quality of Life Questionnaire (AAQOL)
Authors: Rutishauser C. , Sawyer S.M. , Bond L. , Coffey C. , Bowes G.
Published: July 2002

Current asthma-specific quality of life questionnaires have major conceptual and methodological deficiencies for use in adolescents. The aim of this study was to develop and validate the “Adolescent Asthma Quality of Life Questionnaire (AAQOL)”, specifically developed for adolescents with asthma.

One-hundred and eleven adolescents with frequent-episodic or persistent asthma aged 12–17 yrs were recruited from three tertiary paediatric asthma clinics. The standardized multi-step method consisted of: 1) item selection including semistructured interviews (n=14); 2) item reduction and validation (n=66); and 3) assessment of reproducibility (n=31). Item reduction was performed applying the clinical impact method.

The 32 item AAQOL covers six domains: symptoms, medication, physical activities, emotion, social interaction and positive effects. There was high internal consistency for the six domains (α=0.70–0.90) and for the total score (α=0.93). Test-retest reliability was high for all domain scores (r=0.76–0.85) and the total score (r=0.90), indicating high reproducibility of the AAQOL. There was high correlation with the paediatric Asthma Quality of Life Questionnaire (ρ=0.81) which focuses primarily on symptoms and emotional well-being. There was weak to moderate correlation with clinical parameters of asthma severity (ρ=0.25–0.65).

The 32-item Adolescent Asthma Quality of Life Questionnaire is a valid, developmentally age-appropriate and dimensionally comprehensive asthma-specific quality of life measure for use in adolescents.
Plethysmographic measurements of lung volume and airway resistance
Authors: Stocks J. , Godfrey S. , Beardsmore C. , Bar-Yishay E. , Castile R.
Published: July 2002

Functional residual capacity (FRC) is the only static lung volume that can be measured routinely in infants. It is important for interpreting volume-dependent pulmonary mechanics such as airway resistance or forced expiratory flows, and for defining normal lung growth. Despite requiring complex equipment, the plethysmographic method for measuring FRC is very simple to apply and, unlike the gas dilution techniques, enables repeat measures of lung volume to be obtained within a few minutes. This method has the further advantage that with suitable adaptations to the equipment, simultaneous measurements of airway resistance can also be obtained.

The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for plethysmographic measurements in infants. Implementation of these recommendations should help to ensure that such measurements are as accurate as possible and that meaningful comparisons can be made between data collected in different centres or with different equipment. These guidelines cover numerous aspects including terminology and definitions, equipment, data acquisition and analysis and reporting of results and also highlight areas where further research is needed before consensus can be reached.
Reversing acute bronchoconstriction in asthma: the effect of bronchodilator tolerance after treatment with formoterol
Authors: Jones S.L. , Cowan J.O. , Flannery E.M. , Hancox R.J. , Herbison G.P. , Taylor D.R.
Published: July 2002

Continuous treatment with a short-acting β2‐agonist can lead to reduced bronchodilator responsiveness during acute bronchoconstriction. This study evaluated bronchodilator tolerance to salbutamol following regular treatment with a long-acting β2‐agonist, formoterol. The modifying effect of intravenous corticosteroid was also studied.

Ten asthmatic subjects (using inhaled steroids) participated in a randomised, double-blind, placebo-controlled, cross-over study. Formoterol 12 μgb.i.d.or matching placebo was given for 10–14 days with >2 weeks washout. Following each treatment, patients underwent a methacholine challenge to induce a fall in forced expired volume in one second (FEV1) of at least 20%, then salbutamol 100 μg, 100 μg, and 200 μg was inhaledviaa spacer at 5 min intervals, with a further 400 μg at 45 min. After a third single-blind formoterol treatment period, hydrocortisone 200 mg was given intravenously prior to salbutamol. Dose-response curves for change in FEV1with salbutamol were compared using analysis of covariance to take account ofmethacholine-induced changes in spirometry.

Regular formoterol resulted in a significantly lower FEV1after salbutamol at each time point compared to placebo (p<0.01). The area under the curves (AUCs) for 15 (AUC0–15) and 45 (AUC0–45) min were 28.8% and 29.5% lower following formoterol treatment (p<0.001). Pretreatment with hydrocortisone had no significant modifying effect within 2 h of administration.

It is concluded that significant tolerance to the bronchodilator effects of inhaled salbutamol occurs 36 h after stopping the regular administration of formoterol. This bronchodilator tolerance is evident in circumstances of acute bronchconstriction.
Allergic sensitization and diet: ecological analysis in selected European cities
Authors: Heinrich J. , Hölscher B. , Bolte G. , Winkler G.
Published: July 2002

It has been postulated that the prevalence of atopic diseases and their increase over time are associated with regional differences in diet and trends. The results of an ecological correlation study comparing the mean daily intake of selected dietary constituents and the prevalence of allergic sensitization in adults in Europe is presented.

Prevalence data from the European Community Respiratory Health Survey (ECRHS) were used. For eight out of 37 ECRHS centres (including 3,872 subjects), comparable dietary data could be obtained. The effect for each dietary constituent was modelled using logistic regression analyses with a term for over dispersion.

Inverse associations between the prevalence of allergic sensitization and the energy adjusted intake of fruit were found (odds ratio (OR)=0.68, p=0.034). Furthermore OR for energy adjusted intake of vitamin A (OR=0.73, p=0.057), vitamin C (OR=0.83, p=0.338) and riboflavin (OR=0.72, p=0.077) were consistently <1, but confidence intervals were wider. Daily intake of monounsaturated fatty acids (energy adjusted) was positively associated with sensitization prevalence (OR=1.59, p=0.035).

These results support the hypothesis that a high intake of monounsaturated fatty acids might promote the development of allergic sensitization.
Primary ciliary dyskinesia syndrome associated with abnormal ciliary orientation in infants
Authors: Biggart E. , Pritchard K. , Wilson R. , Bush A.
Published: July 2002

Primary ciliary dyskinesia (PCD) syndrome associated with abnormal ciliary orientation but with normal ciliary ultrastructure has been described in adults, but there are no normal ranges for orientation in infants, despite the fact that half of all patients with PCD present in the new-born period.

Nasal brush biopsies were obtained from eight infants (three males), mean age 13.1 months, range 7–23, in order to determine ciliary orientation. They had no upper or lower airway disease and normal organ arrangement and were undergoing general anaesthesia for other reasons. Two infants with typical PCD syndrome but normal ultrastructure of individual cilia also had orientation studies.

In the eight normal subjects, a mean of 254 central pairs was examined, range 82–453. The mean ciliary orientation was 14.9 degrees, range 12.9–17.5. The two infants with PCD syndrome but normal ultrastructure of individual cilia had ciliary orientation of (Case 1) 44.5 degrees (range 10.6–64.5) in 218 central pairs; and on a second occasion, 28.9 degrees, (range 9.0–47.5) in 259 central pairs; for Case 2, 24.4 degrees, (range 13.1–38.4) in 196 central pairs.

The normal range for ciliary orientation is similar in infants to that described in other work in adults. The two cases of phenotypic primary ciliary dyskinesia in the presence of normal ciliary ultrastructure but abnormal ciliary orientation in infants supports the contention that measurement of ciliary orientation should be part of the assessment of ciliary structure and function in cases of possible primary ciliary dyskinesia, in particular when the ultrastructure of individual cilia appear to be normal.
Long-term use of mandibular advancement splints for snoring and obstructive sleep apnoea: a questionnaire survey
Authors: McGown A.D. , Makker H.K. , Battagel J.M. , L'Estrange P.R. , Grant H.R. , Spiro S.G.
Published: July 2002

A mandibular advancement splint (MAS) may be an alternative treatment for snoring and obstructive sleep apnoea (OSA). However, there is little subjective or objective information concerning long-term effectiveness, compliance and side effects.

A retrospective questionnaire was used to survey these issues plus patient satisfaction and maintenance requirements in 166 patients who could have worn a mandibular advancement splint for over a year.

One-hundred and twenty-six (76%) subjects returned the questionnaire, (84 with OSA, 42 snorers), of whom 69 (55%) reported still using the splint regularly, 47 (37%) every night. The most common reported reasons for stopping use were discomfort (29/57; 52% of nonusers), and poor perceived efficacy (12 subjects). Users reported more daytime symptoms, and they and their partners were more likely to observe improvements with splint use. Side effects were reported by 49 subjects, more commonly in nonusers. Sixty-five of 67 current users and 23 of 41 nonusers reported less snoring with splint use (p=<0.001).

Long-term mandibular advancement splint usage appeared less satisfactory than previously reported, however, splints were considered effective by 97% of current users and even by over half of those who had stopped use. Reasons for stopping use included side effects, social circumstances, dental treatment, as well as lack of perceived efficacy.
Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis
Authors: Hermans C. , Petrek M. , Kolek V. , Weynand B. , Pieters T. , Lambert M. , Bernard A.
Published: July 2002

To test the hypothesis that sarcoidosis is associated with an intravascular leakage of lung epithelium secretory proteins, the occurrence and determinants in serum of sarcoid patients of CC16, a small size and readily diffusible lung-specific protein of 16 kDa secreted by bronchiolar Clara cells, was investigated.

CC16 was measured by a sensitive latex immunoassay in the serum of 117 patients with established sarcoidosis and of 117 healthy subjects matched for age, sex and smoking status. Stepwise regression analysis was used to identify extrapulmonary variables of CC16 changes in serum. These changes were then compared with biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF) as well as with the number of CC16 immunostaining cells on bronchial or pulmonary biopsy samples.

CC16 concentration in serum of sarcoid patients was significantly increased, compared to their matched controls (25.9±16.2versus13.9±5.2 µg·L−1). In nonsmoking patients without significant renal impairment, CC16 in serum increased with the severity of the chest radiograph and computed tomography changes, and was on average 50–100% higher when parenchymal involvement was present. Sarcoid patients had, however, normal levels of CC16 in BALF and an unchanged number of CC16-immunopositive cells in lung biopsy samples, suggesting that an increased secretion of CC16 in the sarcoid lung is very unlikely, and that the elevation of CC16 in sarcoidosis results from an increased intravascular leakage of the protein across the air-blood barrier.

The present study suggests that CC16 in serum might provide a useful tool to noninvasively evaluate the damage and increased permeability to proteins of the air-blood barrier associated with sarcoidosis.
Production of oxidants in alveolar macrophages and blood leukocytes
Authors: Haugen TS , Skjonsberg OH , Kahler H , Lyberg T
Published: July 2002

Increased production of oxidants subsequent to phagocyte stimulation has been associated with tissue damage in lung inflammatory disorders. The overall oxidative burden of the lung may vary with inflammatory cell composition. Flow cytometry using three different dyes, dihydroethidium (DHE), dichlorofluorescein diacetate (DCFH-DA) and dihydrorhodamine 123 (DHR), all compounds that by interaction with oxidants are transformed to fluorescent products, was used to examine the production of intracellular oxidants in alveolar macrophages (AMs), including size-defined subpopulations, monocytes (Ms) and polymorphonuclear neutrophils (PMNs) during in vitro incubation in the presence or absence of phorbol myristate acetate (PMA). PMA stimulation led to slightly increased (two-fold) (p<0.05) DHE-induced fluorescence in AMs, whereas it was greatly increased in Ms and PMNs (13-fold and 113-fold, respectively). The levels of DCFH-DA- and DHR-induced fluorescence were significantly (p<0.05) increased (four-fold and 110-fold, respectively) by PMA stimulation of PMNs, but not of AMs and Ms. Significant differences (p<0.05) in the levels of DHE- and DCFH-DA-induced fluorescence in small and large AMs were also demonstrated. The results show that the potential to increase the generation of various oxidants upon stimulation was: PMNs> Ms>AMs, suggesting that the total oxidative burden of the lungs is dependent on the type of inflammatory cells present, as well as on their state of activation.
Human neutrophil lipocalin, a highly specific marker for acute exacerbation in cystic fibrosis
Authors: Eichler I , Nilsson M , Rath R , Enander I , Venge P , Koller DY
Published: July 2002

Cystic fibrosis (CF) is characterized by the production of abnormally thick secretions in the airways, chronic bacterial endobronchial infections and a chronic, predominantly neutrophilic inflammatory response. Therefore, myeloperoxidase (MPO) and lactoferrin are frequently used as inflammatory markers. Recently, a new protein in the neutrophil granules, human neutrophil lipocalin (HNL) has been discovered. The aim of the present study was to investigate HNL in sera of patients with CF and its relation to MPO and lactoferrin as well as to acute pulmonary exacerbation. Serum concentrations of HNL, MPO and lactoferrin were determined in 42 patients with CF and in 25 healthy subjects. Patients with CF were divided into groups with and without acute pulmonary exacerbation (APE) and also with and without colonization with Pseudomonas aeruginosa (Pa). Median serum levels of HNL (200.5 microg x L(-1)), MPO (595 microg x L(-1)) and lactoferrin (1,356.5 microg x L(-1)) were significantly increased in patients with CF compared to control subjects (57.7, 178 and 478 microg x L(-1), respectively; p<0.0001). CF patients with APE had significantly increased serum concentrations of HNL (321 versus 97.7 microg x L(-1); p<0.0001), MPO (1,125 versus 300 microg x L(-1); p<0.005) and lactoferrin (4,936 versus 980 microg x L(-1); p<0.001) compared with patients in stable clinical condition. Similarly, patients colonized with Pa had significantly higher concentrations of HNL, MPO and lactoferrin than Pa negative patients. These results indicate that in patients with cystic fibrosis, serum concentrations of human neutrophil lipocalin are markedly increased with a strong relationship to myeloperoxidase and lactoferrin. Thus, determination of serum human neutrophil lipocalin concentrations may be another useful diagnostic tool to monitor neutrophil inflammation in cystic fibrosis. The more marked difference in human neutrophil lipocalin compared with myeloperoxidase concentrations with no overlap between patients with acute pulmonary exacerbation and those in stable condition even suggests that human neutrophil lipocalin may be a more sensitive and specific discriminator.
An integral equation representation of wide‐band electromagnetic scattering by thin sheets
Authors: Song Yoonho , Kim Hee Joon , Lee Ki Ha
Published: July 2002

An efficient, accurate numerical modeling scheme has been developed, based on the integral equation solution to compute electromagnetic (EM) responses of thin sheets over a wide frequency band. The thin‐sheet approach is useful for simulating the EM response of a fracture system in the earth. The focus of this development has been the accuracy of the numerical solution over a wide‐band frequency range of up to 100 MHz. The effect of displacement currents is included to correctly evaluate high‐frequency EM scattering.

Currently, EM responses of two thin sheets with different geometrical and electrical properties embedded in a three‐layer earth can be modeled over a frequency band of 10−3to 108Hz. The layered earth and the sheets can be electrically dispersive, an important feature that allows analysis of frequency‐dependent characteristics of the model under investigation. The source field can be generated by a remote or local electric or magnetic dipole located on the surface or in a borehole. A plane‐wave source can also be used, and numerical analyses have been made for magnetotellurics and the high‐frequency impedance method.
From acquisition footprints to true amplitude
Authors: Gesbert Stéphane
Published: July 2002

This paper addresses the issue of the sensitivity of 3‐D prestack depth migration (PSDM) with respect to the acquisition geometry of 3‐D seismic surveys. Using the theoretical framework of PSDM, I show how acquisition‐related imaging artifacts—the acquisition footprints—can arise. I then show how the acquisition footprint can be suppressed in two steps by (1) partitioning the 3‐D survey into minimal data sets, each to be migrated separately, and (2) applying a robust variable‐geometry PSDM quadrature. The validity of the method is demonstrated on synthetic parallel and antiparallel multistreamer data and cross‐spread data.

The proposed two‐step solution can play an important role in projects where amplitude integrity and fidelity are paramount, e.g., quantitative interpretation and time‐lapse surveying. The concept of minimal data also fills a gap in understanding the relation between acquisition and imaging.