bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Cost Benefits of Anticoagulation for Stroke Prevention in Atrial Fibrillation Underestimated?
Authors: Miller Paul S.J. , Andersson Fredrik L. , Kalra Lalit
Published: January 2005

Background and Purpose—Stroke outcomes in patients with atrial fibrillation (AF) tend to be worse than those in patients without AF. The objective of this study was to evaluate whether the cost benefits of anticoagulation for stroke prevention in AF may currently be underestimated by existing economic models that do not distinguish between different stroke outcomes.

Methods—A literature review was conducted in 3 areas: (1) studies comparing stroke outcomes in AF and non-AF patients; (2) studies providing long-term cost of stroke estimates; and (3) studies modeling the cost-effectiveness of anticoagulation with a vitamin K antagonist (eg, warfarin) in AF patients.

Results—There is considerable evidence that stroke in AF patients has a worse outcome than in patients without AF, including higher mortality, severity, and recurrence rates, and greater functional impairment and dependency. Estimates of the long-term cost of stroke of different severities were between US $24 991 for a mild stroke over 5 years and US $142 251 for a major ischemic stroke over a lifetime (2004 prices). The cost of a severe ischemic stroke may typically be 3-times that of mild stroke. However, cost-effectiveness models for anticoagulation in patients with AF have used average (not AF-specific) cost-of-stroke data, and most have used stroke severity distributions derived from clinical trials, which may differ from those in clinical practice.

Conclusions—Existing economic models underestimate the cost benefits of anticoagulation for stroke prevention because they do not adjust for poorer outcomes associated with cardioembolic strokes.
A geometric morphometric assessment of the 'batagurine process' of testudinoid turtles
Authors: Russell Anthony , Jamniczky Heather
Published: January 2005

The batagurine process and associated rearward extension of the pterygoid, putative diagnostic characters of the turtle taxon Bataguridae, are evaluated using geometric morphometrics. Visual examination of 28 testudinoid turtles, representing each of the three clades within the taxon, showed the presence of a possible batagurine process and rearward extension of the pterygoid in the majority of specimens, but identification of the batagurine process sensu stricto was not able to be objectively established. Six landmarks on the palatal surface and sets of semi-landmarks on the basioccipital and pterygoid were digitized on photographs of the ventral surface of each skull for geometric morphometric analysis, and subjected to Generalized Procrustes and Relative Warps Analysis. No significant differences in basioccipital, pterygoid or palate shape between the three taxa were found, and the Relative Warps Analysis of the Procrustes coordinates revealed no separation of taxa on relative warps one or two for any of the data sets. The batagurine process and accompanying posterior extension of the pterygoid are thus of questionable phylogenetic utility in the separation of the Bataguridae from other testudinoid turtles.
Local distribution, habitat use, and diet of two supposed 'species' of the Psammophis 'phillipsi' complex (Serpentes: Colubridae), sympatric in southern Nigeria
Authors: Politano Edoardo , Luiselli Luca , Angelici Francesco , Ude Linda , Akani Godfrey , Eniang Edem
Published: January 2005

Snakes of the genus Psammophis are widespread in diverse habitats of west Africa, from dry savannas to moist rainforests. In southern Nigeria, P. phillipsi occurs with two 'forms', one with a divided cloacal shield (CSD) and one with an entire cloacal shield (CSE). These 'forms' were suggested to be possibly distinct species in a recent review by Hughes (1999). However, as no data are available on the variation in natural history, if any, between these two supposed species, we collected data on local distribution and natural history traits of these 'forms' in several localities of southern Nigeria. Out of 32 localities examined, sympatric CSD and CSE specimens occurred in 28.1% of the localities, CSD specimens alone occurred in 68.8%, and CSE specimens alone occurred in 3.1%. At five additional localities, where a higher number of specimens was examined (range 21-41 specimens), CSD specimens were clearly dominant over CSE specimens (on average 88.8% of specimens in each population), independently of the habitat types, and there was no apparent effect of longitude on the frequency of occurrence of CSD specimens. Both 'forms' proved to be habitat generalists (often inhabiting deforested areas and suburbs), and very similar in terms of type of prey eaten (mainly Agama lizards and Mabuya skinks, but also small mammals), and apparently also in terms of micro-habitats used for foraging (clearings into forested zones). Overall, there was no evident difference between these 'forms' in terms of the main ecological traits examined here.
Karyological and osteological data supporting the specific status of Iberolacerta (cyreni) martinezricai (Arribas, 1996)
Authors: Arribas Oscar , Odierna Gaetano
Published: January 2005

Iberolacerta (cyreni) martinezricai has a karyotype of 2n = 36, all acrocentric macrochromosomes. Nucleolar Organizer Regions (NORs) are interstitially situated on a medium small (MS-type) chromosome, a derived character shared with I. cyreni, which differs in details of W-sex chromosome: W is heteromorphic and heterochromatic in I. cyreni, while it is homomorphic and euchromatic in I. (c.) martinezricai. Osteologically, it is characterized by the presence of a triangular-shaped expansion of the squamosal towards the supratemporal fenestra, and by the presence of seven (instead of six) posterior short ribbed presacral vertebrae. These odd characters probably became fixed in this relic taxon by imbreeding. Its differences and affinities are discussed, proposing a specific status for this taxon.
The taxonomic status of Leptognathus incertus Jan, 1863, with revalidation of Dipsas alternans (Fischer, 1885) (Serpentes: Colubridae: Dipsadinae)
Authors: Passos Paulo , Caramaschi Ulisses , Fernandes Daniel
Published: January 2005

The dipsadine snake Leptognathus incertus was originally described from French Guiana and subsequently was restricted to the Atlantic Rain Forest in southeastern and south Brazil. We compare its original description with available data for Leptognathus alternans as well as with species of the genus Dipsas occurring in French Guiana. Leptognathus alternans is revalidated in the combination Dipsas alternans, representing the populations occurring in the Atlantic Rain Forest of southeastern and south Brazil. The neotype of L. alternans is designated and described. The taxonomic status of L. incertus is revised and, in the interest of stabilizing the nomenclature of this species, Dipsas copei is synonymized with L. incertus in the combination Dipsas incerta, corresponding to populations of the Guianan region. The holotype of L. copei is designated as the neotype of L. incertus. A serpente dipsadínea Leptognathus incertus foi descrita originalmente da Guiana Francesa e posteriormente restrita à Floresta Atlântica no sudeste e sul do Brasil. Comparamos sua descrição original com os dados disponíveis de Leptognathus alternans, bem como com espécies do gênero Dipsas que ocorrem na Guiana Francesa. Leptognathus alternans é revalidada sob a combinação Dipsas alternans, representando as populações que ocorrem na Floresta Atlântica do sudeste e sul do Brasil. O neótipo de L. alternans é designado e descrito. O status taxonômico de L. incertus é revisado e, no interesse da estabilização da nomenclatura desta espécie, Dipsas copei é sinonimizada com L. incertus sob a combinação Dipsas incerta, correspondendo às populações da região das Guianas. O holótipo de L. copei é designado como o neótipo de L. incertus.
The Rhetoric and Practice of Self-Determination: A Right of All Peoples or Political Institutions?
Authors: Summers James
Published: January 2005

The right of peoples to self-determination occupies a prominent position in a number of key international instruments, like the Human Rights Covenants and the United Nations Charter. Yet, despite this, many questions remain about the right in international law. This article is an analysis of the right which will look at its language in relation to its practical application. Its focus is on self-determination as a rhetoric, which, it is argued, is used to legitimize political activities by presenting those activities in terms of peoples and their self-realization. It will be further argued that as political rhetoric self-determination is most likely to be invoked in the institutions that direct and provide a focus for political life. This produces the paradox in the right. Although the rhetoric of self-determination suggests that peoples and their characteristics provide the basis for political institutions, the right, in fact, seems to be shaped in large part by those institutions. This, in turn, has important implications for how self-determination should be looked at in relation to other legal principles.
The Emerging International Architecture of Indigenous Rights: The Interaction between Global, Regional, and National Dimensions
Authors: van Genugten Willem , Perez-Bustillo Camilo
Published: January 2005

The article gives an overview of the current status of human rights and poverty in the context of the contemporary struggles of indigenous peoples. It aims to describe the framework of indigenous rights as constituted by, and constitutive of, the relationship between legal processes at the international, regional and national levels. The article also makes links to broader issues such as the racial, ethnic, linguistic and cultural human rights instruments, as well as to the important linkage to international poverty law. It outlines the current status of international legal protection for indigenous peoples before giving different cases in which these legal mechanisms have been used and questioned at the regional and national levels. The article concludes by arguing that indigenous rights standards play an important role in terms of serving as 'ceilings' or 'floors' between which indigenous movements and supporting NGOs can mobilize and find a legal framework to form their case.
Risk, Reflexivity and an Elusory Body
Authors: Wheatley Elizabeth E.
Published: January 2005

This article calls attention to how theory shapes ethnographic relations, practices, and “truths” about bodies and identities. While carrying out ethnographic research among men and women with heart disease, I experienced a “scare” for ovarian cancer, which interrupted the fieldwork, elicited revisions in research relations, and compelled me to see how my theoretic and purposive agendas had functioned as discourses that promoted and reinforced differences between research participants and me. My elusory body enabled me to recognize our fundamental similarities and alerted me to misguided turns I had taken in my research trajectory.
Experiences From the National Institute of Nursing Research: Summer Genetics Institute 2004
Authors: Whitt Karen J.
Published: January 2005

The National Institute of Nursing Research (NINR) Summer Genetics Institute (SGI) prepares nurses with training in molecular genetics for use in clinical practice, research, and education. Experiences from the SGI 2004 are recounted. More than 35 genetic experts from National Institutes of Health and surrounding universities in Washington, D.C., provided lecture and laboratory experiences. The lecture portion of the SGI focused on the molecular aspect of genetics and the laboratory component included experiments designed to provide an understanding of genetic approaches for diagnostic and research purposes. The SGI prepares nurses with the genetic foundation to meet the healthcare challenges of the future.
Transcendent Pluralism and the Influence of Nursing Testimony on Environmental Justice Legislation
Authors: Perry Donna
Published: January 2005

Environmental justice is an important issue affecting health disparities. Using the framework of transcendent pluralism, this article describes nursing actions and research in a legislative coalition for an environmental justice bill. Two descriptive studies are conducted: a focus group with six legislative aides and an evaluation of a nursing presentation given to 10 Massachusetts state legislators. Pretest and posttest results showed a small but significant increase in the legislators’ disposition toward the bill; the mean score increased from 5.4 to 5.9 (p = .037). Legislators perceived nurses as lobbying more for nursing profession issues than general health issues (score of 6.3 vs. 4.6; p = .009). Guidelines for lobbying that emerged from the data are included. The author argues that nursing knowledge should play a vital role in public policy and that nurses need to broaden their efforts beyond professional issues to the larger issues that influence a healthy human society.
Failure of montelukast to reduce sputum eosinophilia in high-dose corticosteroid-dependent asthma
Authors: Jayaram L. , Duong M. , Pizzichini M. M. M. , Pizzichini E. , Kamada D. , Efthimiadis A. , Hargreave F. E.
Published: January 2005

Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment. Montelukast is a cysteinyl leukotriene antagonist, which also reduces sputum and blood eosinophils. The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant.

A total of 14 clinically stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone, with baseline sputum eosinophilia (≥5%), were randomised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial. The primary outcome was the effect of treatment on the percentage of sputum eosinophils. Secondary outcomes were changes in the blood eosinophil count, symptoms, forced expiratory volume in one second, peak expiratory flow and the need for salbutamol.

The median (interquartile range,i.e.75th–25th centile) for sputum eosinophils at baseline was 15.7% (22). The effect of adding montelukast was not significantly different from that of placebo, sputum eosinophils being 9.3% (18.9) after montelukast and 11.3% (22.8) after placebo. No difference was detected on secondary outcomes. No crossover interactions were observed.

In conclusion, the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia.
A randomised trial to evaluate the self-administered standardised chronic respiratory questionnaire
Authors: Schünemann H. J. , Goldstein R. , Mador M. J. , McKim D. , Stahl E. , Puhan M. , Griffith L. E. , Grant B. , Austin P. , Collins R. , Guyatt G. H.
Published: January 2005

The original chronic respiratory questionnaire (CRQ), one of the most widely used measures of health-related quality of life (HRQL) in chronic respiratory disease (CRD), is traditionally interviewer administered (IA) and includes an individualised dyspnoea domain. The present authors studied the impact of self-administered (SA) and standardised dyspnoea questions on CRQ measurement properties.

In a factorial design multicentre trial, 177 patients with CRD (mean age 67.7 yrs; mean forced expiratory volume in one second per cent predicted 44.6%) were randomised to CRQ-IA (n = 86) or CRQ-SA (n = 91), and to initially complete the standardised or individualised items before and after respiratory rehabilitation.

While maintaining validity, the CRQ-SA proved more responsive to changes in HRQL than the CRQ-IA in all domains. Compared with the standardised dyspnoea domain, the individualised dyspnoea domain indicated greater responsiveness. The correlations of baseline scores and change scores with other HRQL instruments indicated good validity of the CRQ-SA.

In conclusion, self-administration and standardisation of the chronic respiratory questionnaire maintains validity and responsiveness relative to the interviewer-administered chronic respiratory questionnaire. These results challenge the assumption that interviewer-administered questionnaires are superior to self-administered questionnaires in older patients with chronic respiratory disease.
Neutrophils, interleukin-17A and lung disease
Authors: Lindén A. , Laan M. , Anderson G. P.
Published: January 2005

It is now established that an excessive and sustained mobilisation of neutrophils is a hallmark of several chronic inflammatory lung disorders, including severe obstructive lung disease. This article reviews evidence that the cytokine interleukin (IL)-17A is a major orchestrator of sustained neutrophilic mobilisation.

Current evidence suggests that IL-17A is produced by T-lymphocytes, and that it exerts an orchestrating effect on the accumulation and associated activity of neutrophils in the bronchoalveolar space indirectly, through an induced release of specific cytokines and colony-stimulating factors in resident lung cells.

Although the involvement of IL-17A in inflammatory lung disorders is supported by several recent studies, its causative role is still uncertain.

However, the unique position of interleukin-17A at the interface between acquired and innate immunity puts this cytokine forward as an important signal for the reinforcement of host defence; it also implies that interleukin-17A may constitute a useful target for pharmacotherapeutic intervention.
Association of clinical features with HLA in chronic pulmonary thromboembolism
Authors: Tanabe N. , Kimura A. , Amano S. , Okada O. , Kasahara Y. , Tatsumi K. , Takahashi M. , Shibata H. , Yasunami M. , Kuriyama T.
Published: January 2005

The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown and may be heterogeneous, because there are several ethnic differences in the clinical characteristics of CTEPH. Female predominance and a higher ratio of chronic to acute pulmonary thromboembolism have been reported in Japan as compared with the USA. Because such ethnic differences may be controlled by genetic factors, the current study investigated HLA polymorphisms in Japanese patients with CTEPH.

HLA typing by serological and/or DNA typing methods was performed (for HLA-A, B, DPB1, DRB1) in 80 patients and 678 controls, and the association of clinical characteristics with HLA alleles was studied.

The frequencies of HLA-B*5201 (40versus24%) and DPB1*0202 (19versus6%) were significantly higher in the patients. HLA-B*5201 positive patients showed a significant female predominance. Total pulmonary vascular resistance and mixed venous oxygen tension were better in the HLA-B*5201 positive patients. In contrast, cardiac index and gas exchange parameters were worse in the HLA-DPB1*0202 positive patients. In the patients carrying HLA-B*5201 and/or -DPB1*0202, the frequency of deep vein thrombosis was significantly lower than the other patients.

These observations suggested that both the susceptibility and clinical characteristics of chronic thromboembolic pulmonary hypertension were controlled in part by the HLA-B and -DPB1 loci.
Duration of RT-PCR positivity in severe acute respiratory syndrome
Authors: Chu C. M. , Leung W. S. , Cheng V. C. C. , Chan K. H. , Lin A. W. N. , Chan V. L. , Lam J. Y. M. , Chan K. S. , Yuen K. Y.
Published: January 2005

Severe acute respiratory syndrome (SARS) is a highly infectious respiratory infection with a high mortality. The duration of infectivity is unknown. The RT-PCR positivity for SARS-associated coronavirus (SARS-CoV) was followed in 45 virologically confirmed SARS patients.

Serial RT-PCRs for SARS-CoV were performed in the nasopharyngeal aspirate, stool and urine of 45 SARS patients who survived until discharge. All patients had at least one site that was positive for SARS-CoV on presentation. Time to RT-PCR conversion was studied in all patients.

There were 15 males (33.3%) and 30 females (66.7%), with a mean±sdage of 40.7±14.7 yrs. The median (range) time of RT-PCR conversion was 30 days (2–81). On discharge from the hospital, 18 (40%) remained RT-PCR positive in at least one site. For patients with positive RT-PCR on discharge, the median (range) time to RT-PCR conversion after discharge was 13 days (2–60).

A significant proportion of severe acute respiratory syndrome patients remained RT-PCR positive for severe acute respiratory syndrome-associated coronavirus for a substantial duration after discharge. The clinical significance is unknown and this finding merits further study. It is prudent to advise patients to adhere to strict personal hygiene on discharge until RT-PCR becomes negative.
Different lung responses to cigarette smoke in two strains of mice sensitive to oxidants
Authors: Bartalesi B. , Cavarra E. , Fineschi S. , Lucattelli M. , Lunghi B. , Martorana P. A. , Lungarella G.
Published: January 2005

The development of cigarette smoke-induced pulmonary changes in C57 Bl/6J and DBA/2 mice was investigated. Both strains are sensitive to oxidants and C57Bl/6J mice are moderately deficient in serum alpha1-proteinase inhibitor.

Following chronic exposure to cigarette smoke, patchy emphysema was present in mice of both strains, but developed faster in DBA/2 mice. A positive reaction for mouse neutrophil elastase was seen on the septa of both strains. Additionally, the DBA/2 mice developed a uniform parenchymal dilation that was preceded by the appearance of apoptotic cells in areas with a low signal for vascular endothelial growth factor-receptor 2. Fibrotic areas scattered throughout the parenchyma, coupled with a positive immunohistochemical reaction for transforming growth factor-β was seen only in DBA/2 mice.

Both DBA/2 and C57Bl/6J strains showed epithelial cell injury and areas of deciliation in their airways. However, the appearance of goblet cell metaplasia was common in C57Bl/6J mice but rare in DBA/2 mice. A positive immunohistochemical reaction for interleukin (IL)-4, IL-13 and MUC5AC was seen only in the airways of C57Bl/6J mice.

Strain characteristics (alpha1-proteinase inhibitor levels, sensitivity to oxidants, and constitutive levels of vascular endothelial growth factor-receptor 2) and phenotypical responses (apoptosis and cytokine distribution) may condition parenchymal and airway changes to cigarette smoke.
Quantitative computed tomography and aerosol morphometry in COPD and α1-antitrypsin deficiency
Authors: Shaker S. B. , Maltbaek N. , Brand P. , Haeussermann S. , Dirksen A.
Published: January 2005

Relative area of emphysema below -910 Hounsfield units (RA-910) and 15th percentile density (PD15) are quantitative computed tomography (CT) parameters used in the diagnosis of emphysema. New concepts for noninvasive diagnosis of emphysema are aerosol-derived airway morphometry, which measures effective airspace dimensions (EAD) and aerosol bolus dispersion (ABD).

Quantitative CT, ABD and EAD were compared in 20 smokers with chronic obstructive pulmonary disease (COPD) and 22 patients with α1-antitrypsin deficiency (AAD) with a similar degree of airway obstruction and reduced diffusion capacity.

In both groups, there was a significant correlation between RA-910 and PD15 and pulmonary function tests (PFTs). A significant correlation was also found between EAD, RA-910 and PD15 in the study population as a whole. Upon separation into two groups, the significance disappeared for the smokers with COPD and strengthened for those with AAD, where EAD correlated significantly with RA-910 and PD15. ABD was similar in the two groups and did not correlate with PFT and quantitative CT in either group.

In conclusion, based on quantitative computed tomography and aerosol-derived airway morphometry, emphysema was significantly more severe in patients with α1-antitrypsin deficiency compared with patients with usual emphysema, despite similar measures of pulmonary function tests.
Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension
Authors: Meyer F. J. , Lossnitzer D. , Kristen A. V. , Schoene A. M. , Kübler W. , Katus H. A. , Borst M. M.
Published: January 2005

Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking.

This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II–IV. Mean±sdpulmonary artery pressure was 48.6±16.9 in females and 53.1±22.9 mmHg in males; cardiac output was 3.7±1.3 and 4.2±1.7 L·min−1.

Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3±2.0versus8.2±2.0 kPa). In the male patients,PI,max was lower than in 25 controls (6.8±2.2versus10.5±3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2±2.6versus9.5±2.1 kPa), and in male patients as compared to controls (7.1±1.6versus10.3±3.9 kPa). There was no correlation betweenPI,max orPE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration andPI,max was higher in IPAH than in controls (females 0.067±0.066versus0.021±0.008; males 0.047±0.061versus0.023±0.016).

In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.
The timed walk test as a measure of severity and survival in idiopathic pulmonary fibrosis
Authors: Hallstrand T. S. , Boitano L. J. , Johnson W. C. , Spada C. A. , Hayes J. G. , Raghu G.
Published: January 2005

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease with a median survival of ∼3 yrs. Measurements of airflow and lung volumes at rest are generally used to monitor the clinical course in this disorder. This study was designed to determine if a modified version of the 6-min walk test, called the timed walk test, accurately characterises disease severity and survival in IPF.

The study population consisted of 28 patients with well-characterised progressive IPF. The timed walk test and concurrent measures of disease severity were assessed at baseline. Participants were prospectively followed for ≥4 yrs to determine the relationship between parameters of the timed walk test and survival.

There were strong correlations between the end-exercise saturation and walk-velocity parameters of the timed walk test and diffusing capacity, and arterial oxygen tension at rest. In univariate Cox proportional-hazards models, end-exercise saturation, change in saturation with exercise, walk distance and walk velocity were associated with survival. In unadjusted logistic regression models, odds of death at 2 yrs were associated with the same parameters.

In conclusion, the timed walk test relates to disease severity and long-term outcome in progressive idiopathic pulmonary fibrosis.
Antibiotic therapy reduces nitrosative stress and programmed cell death in the rabbit foetal lung
Authors: Gras-Le Guen C. , Jarry A. , Vallette G. , Toquet C. , Colombeix C. , Laboisse C. L. , Potel G. , Roze J-C. , Bugnon D. , Debillon T.
Published: January 2005

The correlation of clinical and epidemiological data suggests that intrauterine infection/inflammation can promote foetal lung injury.

The aim of this study was: 1) to characterise the early inflammatory response elicited in infected foetal lungs, in terms of nitric oxide-derived oxidative stress and programmed cell death; and 2) to investigate the effects of antibiotic therapy on these parameters.

A previously described rabbit experimental model of materno-foetal infection was used. Animals were divided into three groups: controls;Escherichia coliinfected (12 h); andE. Coliinfected (12 h) and treated (24 h gentamicin+ceftriaxone). Foetal lungs were examined in terms of histology, nitric oxide synthase (NOS) activity, immunohistochemical detection of 3-nitrotyrosine, and detection of apoptotic cells by the TUNEL assay and Hoechst staining.

In the infected group, a moderate inflammatory response was observed, associated with a significant increase in inducible NOS activity, the formation of 3-nitrotyrosine residues in epithelial and immune cells, the down-regulation of constitutive NOS activity and clusters of apoptotic cells, as compared with the control group. Early antibiotic therapy, initiated at 12 h post-inoculation, elicited a significant decrease in the infection-induced nitrosative stress. Levels of 3-nitrotyrosine and of apoptotic cells were decreased in the infected-and-treated group compared with the infected group, mainly by the re-expression of constitutive NOS and of the basal level of inducible NOS.

Altogether, these findings indicate that early antibiotic therapy can curb the inflammatory reaction and help avert antenatal lung injury, which is known to be involved in the onset of bronchopulmonary dysplasia.
HIV-1 Nef mediates post-translational down-regulation and redistribution of the mannose receptor
Authors: Vigerust David J , Egan Brian S , Shepherd Virginia L
Published: January 2005

Human immunodeficiency virus (HIV) has derived a variety of means to evade the host immune response. HIV-derived proteins, including Tat, Nef, and Env, have all been reported to decrease expression of host molecules such as CD4 and major histocompatibility complex I, which would assist in limiting viral replication. The mannose receptor (MR) on the surface of macrophages and dendritic cells (DC) has been proposed to function as an effective antigen-capture molecule, as well as a receptor for entering pathogens such as Mycobacterium tuberculosis and Pneumocystis carinii. Regulation of this receptor would therefore benefit HIV in removing an additional arm of the innate immune system. Previous work has shown that MR function is reduced in alveolar macrophages from HIV-infected patients and that surface MR levels are decreased by the HIV-derived protein Nef in DC. In addition, several laboratories have shown that CD4 is removed from the surface of T cells in a manner that might be applicable to decreased MR surface expression in macrophages. In the current study, we have investigated the role of Nef in removing MR from the cell surface. We have used a human macrophage cell line stably expressing the MR as well as human epithelial cells transiently expressing CD4 and a unique CD4/MR chimeric molecule constructed from the extracellular and transmembrane domains of CD4 and the cytoplasmic tail portion of the MR. We show that the MR is reduced on the cell surface by ∼50% in the presence of Nef and that the MR cytoplasmic tail can confer susceptibility to Nef in the CD4/MR chimera. These data suggest that the MR is a potential intracellular target of Nef and that this regulation may represent a mechanism to further cripple the host innate immune system.
Relation of markers of inflammation (C-reactive protein, white blood cell count, and lipoprotein-associated phospholipase A2) to the ankle brachial index
Authors: Santos Simone , Rooke Thom W , Bailey Kent R , McConnell Joseph P , Kullo Iftikhar J
Published: January 2005

Markers of inflammation are predictive of cardiovascular events but their association with atherosclerotic burden remains poorly defined. We hypothesized that markers of inflammation, including C-reactive protein (CRP), white blood cell (WBC) count, and lipoprotein-associated phospholipase A2 (Lp-PLA2), would be associated with the ankle-brachial index (ABI), a marker of atherosclerotic burden. Subjects were 247 patients referred for lower extremity arterial evaluation to the non-invasive vascular laboratory excluding those with active infection or lower extremity revascularization within the previous year. ABI was measured at two sites in both legs and the lowest of four measurements was used in the analyses. CRP was measured by a high-sensitivity immunoturbidimetric assay and Lp-PLA2 was measured by ELISA. The mean patient age was 68±11 years, and 54% were men. Mean ABI was 0.84-0.31 and 49% had an ABI < 0.9. Age, hypertension, fasting plasma glucose, and ‘ever’ smoking were independently associated with the ABI. Spearman correlation coefficients of inflammatory markers with the ABI were: CRP (r 1/4-0.15, p 1/4-0.02), WBC count (r 1/4-0.27, p 1/4-0.001), and Lp-PLA2 (r 1/4-0.09, p 1/4-0.21). In a multiple regression model that included conventional risk factors and statin use, CRP and WBC count were no longer significantly associated with ABI, whereas Lp-PLA2 was a borderline-significant predictor of lower ABI (p 1/4-0.05). These data indicate that CRP and WBC count are not independently associated with ABI, a marker of atherosclerotic burden in subjects referred for non-invasive lower extremity arterial evaluation. The association of Lp-PLA2 with ABI merits further study.
Plasma levels of cell adhesion molecules during hyperinsulinemia and modulation of vasoactive mediators
Authors: Cardillo Carmine , Mettimano Marco , Mores Nadia , Koh Kwang K , Campia Umberto , Panza Julio A
Published: January 2005

Endothelial expression of cell adhesion molecules (CAMs) plays an important role in atherosclerosis. Atherosclerosis is increased in hyperinsulinemic states, but whether insulin per se is proatherogenic remains unclear. To investigate the effects of hyperinsulinemia on CAM expression, plasma levels of ICAM-1, VCAM-1 and E-selectin were measured before and after forearm infusion of insulin in healthy subjects. Insulin administration for 2 h resulted in signifi-cant hyperinsulinemia, whereas no significant change was observed in soluble CAMs (all p > 0.05). Because insulin stimulates endothelial release of both endothelin-1 (ET-1) and nitric oxide (NO), which may modulate the expression of CAMs, we also investigated the response of CAMs to ET-1 receptor blockade, alone and in combination with NO synthesis inhibition. ET-1 receptor blockade during hyperinsulinemia resulted in a vasodilator response, but did not affect soluble CAMs (all p > 0.05). Superimposition of NO inhibition by l-NMMA reversed the vasodilator effect of ET-1 blockade, without affecting soluble CAMs (all p > 0.05). In conclusion, acute hyperinsulinemia, alone or during ET-1 and NO pathway blockade, does not affect soluble CAMs. These results do not support a direct effect of insulin on endothelial cells to affect leukocyte adhesiveness to the vascular wall.
Vertebral artery dissection following intravascular catheter placement: a case report and review of the literature
Authors: Yu Nicholas R , Eberhardt Robert T , Menzoian James O , Urick Courtney L , Raffetto Joseph D
Published: January 2005

Vertebral artery dissections (VAD) are known to occur as a result of mechanical manipulations of the cervical region, traumatic injury, iatrogenic injury and are also known to arise spontaneously. We report a case of vertebral artery dissection following vertebral artery cannulation during a central line placement and review the literature. The patient underwent intravascular catheter placement that subsequently demonstrated arterial blood. Duplex ultrasound and computed tomographic (CT) scan confirmed vertebral artery cannulation. The catheter was removed at the bedside with pressure, and a subsequent duplex ultrasound scan revealed a vertebral artery dissection. There were no neurological sequelae. The patient was successfully anticoagulated with warfarin but died from unrelated complications. This case report describes the rare iatrogenic event of VAD and reviews its etiology, diagnosis, complications, and management.
Cancer Screening in Theory and in Practice
Authors: Brawley Otis W. , Kramer Barnett S.
Published: January 2005

Improvements in technology have led to a number of tests that can be used to suggest that a patient has a cancer. Advances in cancer biology and medical imaging have led to a number of cancer screening tests. Cancer screening is commonly advocated, but its complexity is often lost in guidelines that have sound-bite quality. It is commonly viewed as of no harm, when in fact there are harms associated with every known screening test. Indeed, many screening experts believe a screening test should only be used when the potential for benefit clearly outweighs the potential for harm.

Cancer screening principles are classically within the realm of the epidemiologist. As more screening tests are developed, these principles have become more relevant to the practicing clinician. What is known and what is unknown about screening is distinctly different from what is believed by the public and many practicing clinicians.

Many tests have both screening and diagnostic uses, and it is only the context in which these are used that determines whether they are screening or diagnostic. A screening test is done on asymptomatic individuals who receive the test principally because they are of the age or sex at risk for the cancer. A diagnostic test is done on an individual because of clinical suspicion of disease.
Surgical Prevention of Cancer
Authors: Bertagnolli Monica M.
Published: January 2005

There have been many recent advances in cancer prevention, including improved understanding of cancer biology, better characterization of premalignant disease, significant advances in cancer surveillance, and identification of effective chemoprevention regimens. Despite this, surgery remains the best option for many individuals at high risk of cancer. Like all prevention modalities, surgical prevention involves balancing the factors governing cancer risk with the benefits and risks of treatment. The issues governing decision making for surgical prevention vary widely among different cancer types, and include consideration of the age and level of cancer risk of the individual, the effectiveness of cancer surveillance for the particular organ at risk, the aggressiveness of the cancer once present, and the morbidity of surgery. This article briefly reviews the use of surgery to prevent some of the most common epithelial malignancies, as well as some of the genetic cancer syndromes for which surgery plays an important role in improving survival.
Oral Cancer Prevention and the Evolution of Molecular-Targeted Drug Development
Authors: Lippman Scott M. , Sudbø Jon , Hong Waun Ki
Published: January 2005

The multifaceted rationale for molecular-targeted prevention of oral cancer is strong. Oral cancer is a major global threat to public health, causing great morbidity and mortality rates that have not improved in decades. Oral cancer development is a tobacco-related multistep and multifocal process involving field carcinogenesis and intraepithelial clonal spread. Biomarkers of genomic instability, such as aneuploidy and allelic imbalance, can accurately measure the cancer risk of oral premalignant lesions, or intraepithelial neoplasia (IEN). Retinoid–oral IEN studies (eg, of retinoic acid receptor-beta, p53, genetic instability, loss of heterozygosity, and cyclin D1) have advanced the overall understanding of the biology of intraepithelial carcinogenesis and of preventive agent molecular mechanisms and targets—important advances for monitoring preventive interventions and assessing cancer risk and pharmacogenomics. Clinical management of oral IEN varies from watchful waiting to complete resection, although complete resection does not prevent oral cancer in high-risk patients. New approaches, such as interventions with molecular-targeted agents and agent combinations in molecularly defined high-risk oral IEN patients, are urgently needed to reduce the devastating worldwide consequences of oral cancer.
Pituitary Transcription Factor-1 Induces Transient Differentiation of Adult Hepatic Stem Cells into Prolactin-Producing Cells in Vivo
Authors: Lee Eun Jig , Russell Theron , Hurley Lisa , Jameson J. Larry
Published: January 2005

A subset of transcription factors function as pivotal regulators of cell differentiation pathways. Pituitary transcription factor-1 (Pit-1) is a tissue-specific homeodomain protein that specifies the development of pituitary somatotropes and lactotropes. In this study, adenovirus was used to deliver rat Pit-1 to mouse liver. Pit-1 expression was detected in the majority (50–80%) of hepatocyte nuclei after tail vein injection (2 × 109 plaque forming units). Pit-1 activated hepatic expression of the endogenous prolactin (PRL), GH, and TSHβ genes along with several other markers of lactotrope progenitor cells. Focal clusters (0.2–0.5% of liver cells per tissue section) of periportal cells were positive for PRL by immunofluorescent staining. The PRL-producing cells also expressed proliferating cell nuclear antigen as well as the hepatic stem cell markers (c-Kit, Thy1, and cytokeratin 14). These data indicate that Pit-1 induces the transient differentiation of hepatic progenitor cells into PRL-producing cells, providing additional evidence that transcription factors can specify the differentiation pathway of adult stem cells.
End fixity to spiral strands undergoing cyclic bending
Authors: Raoof M , Davies T. J
Published: January 2005

Based on a semi-empirical approach and guided by the previously reported experimental observations and theoretical work by the first author, it is suggested that for spiral strands with mean axial strains εc > 0.0025 and outside diameters d ≤ 40 mm, plane-section bending may reasonably be assumed in the course of theoretically determining the deflected shape, of the strands in the immediate vicinity of fixed end(s) with the proviso that, at the assumed ideal fixed end(s) to the spiral strands, ρ/d > 630, where ρ is the estimated minimum radius of curvature at the fixed end. It is also shown that, in practice, the effective fixed end to the spiral strands undergoing such cyclic bending is located not at the face of the zinc-socketed termination, but well within the socket itself; for an axially preloaded spiral strand of 39mm outside diameter, the effective point of end fixity is shown to be located inside the conical housing, about 60mm (or, say, 1.5 diameters) away from the face of the socket. The practical implications of the present findings as regards the traditional approach(es) for determining the minimum radii of curvature at the theoretically assumed (ideal) fixed end, the exact location of which in practice has invariably not (in the previous literature) been properly defined, are critically discussed with such estimated magnitudes of minimum radii of curvature often used as an input into various available models for design against spiral strand restrained bending fatigue. It is, perhaps, worth mentioning that, in the present terminology, the term 'spiral strand restrained bending fatigue’ refers to those cases whereby strand fatigue failures near partially (or fully) restrained terminations of various types occur as a result of cyclic bending of the strand at the termination due to, for example, hydrodynamic or aerodynamic loading.
Tetanus: the ’forgotten disease’. A rare cause of dysphagia and trismus
Authors: Tahery Jawed , Morris David P. , Birzgalis Andrew R.
Published: January 2005

Tetanus kills approximately 500 000 people worldwide each year. Widespread immunization has ensured that it is rarely encountered in the United Kingdom. An increase in global travel may increase the likelihood of such encounters in the developed world in the future.

In the non-immunized patient, death from tetanus can be avoided by early recognition and timely intervention. The potential need for airway support and sedation should not be underestimated.

The authors’ case report should increase the awareness of the otolaryngologist when confronted with atypical cases of dysphagia and trismus and provides details of the recommended treatment regime.
Paediatric retropharyngeal abscess
Authors: Philpott C.M. , Selvadurai D. , Banerjee A.R.
Published: January 2005

Retropharyngeal abscess (RPA) is an uncommon condition with the potential for significant morbidity and mortality if not detected early. The authors present a case report of a 19-month-old child who presented with the common clinical features of a retropharyngeal abscess and in whom the diagnosis was not established by examination and ultrasonography. This led to a delay in appropriate management until a computed tomography (CT) scan was performed under general anaesthesia. The scan demonstrated the diagnosis and surgical drainage was performed under the same anaesthetic. The child subsequently made a complete recovery. The investigation and treatment of RPAs is a matter of some debate and the authors review the recent literature to determine the best management strategy.
Massive retropharyngeal lymphadenopathy in an infant: an unusual presentation of infectious mononucleosis
Authors: Lobo Sudhir , Williams H. , Singh V.
Published: January 2005

Infectious mononucleosis causing upper airway obstruction due to tonsillar disease and associated lymphadenopathy in adolescents is well recognized. However, infection with Epstein-Barr virus (EBV) in a young child of six months is rare. The authors present such a case, with massive swelling of the retropharyngeal lymph nodes, that has not been published previously. The patient presented to this department with a short history of an upper respiratory tract infection and mild upper airway obstruction. On examination there was a massive enlargement of the retropharyngeal space with a compromised airway. This was confirmed on X-ray. She made an uneventful recovery following incision and drainage and a short period of endotracheal intubation. Because of the presence of retropharyngeal lymphoid tissue in infancy an alternative site of upper airway obstruction may occur here in this age group.
Pseudosarcomatous fibrovascular proliferative tissue masquerading as a primary subglottic angiosarcoma
Authors: Persaud Ricardo , Vahidova Dil , Kirsch Claudia , Calaminici Maria , Ghufoor Khalid
Published: January 2005

A unique case of pseudosarcomatous fibrovascular proliferative tissue causing biphasic stridor and simulating a primary subglottic angiosarcoma is reported.

The patient presented with a wheeze and was diagnosed initially with asthma. He subsequently developed worsening biphasic stridor. Flexible nasendoscopy revealed a subglottic mass obstructing the airway. The mass was removed with a carbon dioxide laser and the patient’s condition improved dramatically. The specimen was difficult to interpret histologically and was thought at first to be a novel case of a primary subglottic angiosarcoma. However, the slides were reviewed by expert soft tissue pathologists in the UK and USA, and a final diagnosis of a pseudosarcomatous fibrovascular proliferative lesion was made.

This case highlights the important principle of seeking additional opinions before making a malignant diagnosis in an atypical site. Our report also emphasizes the importance of good clinico-pathological liaison, especially in difficult cases.
Transpalatal endoscopic resection of residual nasopharyngeal carcinoma after sequential chemoradiotherapy
Authors: Roh Jong-Lyel
Published: January 2005

Residual or recurrent nasopharyngeal carcinoma (NPC) is usually managed by re-irradiation or salvage surgery. This case presented a residual NPC with limited extent and an accessible location in the nasopharynx after completion of sequential chemoradiotherapy. The lesion was completely resected via the transpalatal route under endoscopic visualization with no significant post-operative morbidity. This is the first report of NPC successfully treated by this type of surgery.