bluuebunny/crossref_metadata_2025 huggingface dataset:
Surfactant function in children with chronic airway inflammation
Authors: Braun A. , Steinecker M. , Schumacher S. , Griese M.
Published: August 2004

Pulmonary surfactant is necessary to keep the terminal conducting airways patent. It is unknown whether mild to moderate airway inflammation may influence surfactant function and thus contribute to the pathogenesis of chronic airway inflammation in children. To answer this question, 21 children with chronic obstructive bronchitis and 19 asymptomatic children with long-term tracheostomy and increased numbers of neutrophils in their airways were compared with 15 healthy controls. Bronchoalveolar lavage fluid was separated into large surfactant aggregates (LA) and a supernatant containing inhibitory constituents. Surfactant function of LA, recombinations of LA and supernatant, and recombinations of a defined bovine surfactant and supernatant was assessed in a capillary surfactometer. Compared with controls, the function of the LA surfactant was reduced and there was no difference between children with tracheostomy and chronic obstructive bronchitis. The function of LA-supernatant recombinations was poor in all subjects. This may be explained by the well-known protein influx during the lavage procedure. The activity of bovine surfactant-supernatant reconstitutions was impaired in children with tracheostomy. In all surfactant mixtures assessed, surfactant function was inversely correlated to the number of neutrophils in the lavage fluid. Chronic lower airway inflammation with mild or no clinical symptoms is associated with impaired surfactant function. The dysfunction may contribute to airflow restrictions frequently observed in these children.
Background Synaptic Activity Modulates the Response of a Modeled Purkinje Cell to Paired Afferent Input
Authors: Santamaria Fidel , Bower James M.
Published: August 2004

We studied the possible effects of background excitatory and inhibitory synaptic activity on Purkinje cell responses to paired pulse inputs using a morphologically and physiologically detailed compartmental model. Paired-pulse inputs were provided via synapses associated with the ascending segment of the granule cell axon in the presence of variable amounts of background synaptic input provided by parallel fibers and inhibitory interneurons. The results predict the amplitude and dynamics of the somatic and dendritic responses to paired ascending segment inputs are modulated by the level of background synaptic activity, the basal somatic firing rate of the Purkinje cell model does not indicate the type or degree of modulation, and the modulatory effects are mediated through dendritic calcium and calcium-activated potassium currents. These results have important consequences for the functional organization of cerebellar cortex as well as the more general issue of the modulatory as distinct from driving effects of synapses now also being considered in other regions of the mammalian brain including the cerebral cortex.
Here We Are: Social Theatre and Some Open Questions about Its Developments
Authors: Schininá Guglielmo
Published: August 2004

One of the leaders of the movement considers some of the theoretical and historical sources and themes of social theatre as an instrument of action and healing.
One Hand, Many Fingers
Authors: Schechner Richard
Published: August 2004

Schechner's working visit to Taipei, Hong Kong, and Shanghai proved to be a journey among three very different kinds of Chinese communities with very different political and artistic practices—from social drama to traditional theatre.
Art in a Democracy
Authors: Cocke Dudley
Published: August 2004

Reflecting on 25 years of making grassroots art, Cocke asks: How can artists relate to tradition, pursue intercultural collaborations, build diverse audiences, and help communities discover and perform their stories?
Taking Hostages: Staging Human Rights
Authors: Heritage Paul
Published: August 2004

Inside a São Paulo prison, theatre workers and prisoners stage performances proclaiming human rights in order to combat the dehumanizing conditions that feed abuses within the prison system.
ACTing: The pandies' theatre of Delhi
Authors: Kumar Sanjay
Published: August 2004

A New Delhi feminist theatre of children, women, slum-dwellers, and the homeless named after the first Indian to kill his British superior in the 1857 uprising against British rule.
The Playwright in Residence: A Community's Storyteller
Authors: Fisher Amanda Stuart
Published: August 2004

What are the ways that collective storytelling becomes a community-forming activity, where individual and communal identity is negotiated and explored? What are the interactive exchanges between the storyteller and community?
Digging up Stories: An Archaeology of Theatre in War
Authors: Thompson James
Published: August 2004

What happens when the theatre is implicated in the horrors of the situation it displays? Who can judge the truth of one story against another? Should we champion a narrative that denies the rhetoric of war, and deny the narrative that champions the need for war?
Transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria
Authors: Sloand Elaine M. , Mainwaring Lori , Keyvanfar Keyvan , Chen Jichun , Maciejewski Jaroslaw , Klein Harvey G. , Young Neal S.
Published: August 2004

In paroxysmal nocturnal hemoglobinuria (PNH), an acquired mutation of the PIGA gene results in the absence of glycosylphosphatidylinositol (GPI)–anchored cell surface membrane proteins in affected hematopoietic cells. Absence of GPI-anchored proteins on erythrocytes is responsible for their increased sensitivity to complement-mediated lysis, resulting in hemolytic anemia. Cell-to-cell transfer of CD55 and CD59, 2 GPI-anchored proteins, by red cell microvesicles has been demonstrated in vitro, with retention of their function. Because red cell units stored for transfusion contain many erythrocyte microvesicles, transfused blood could potentially serve as a source of CD55 and CD59. We examined whether GPI-anchored proteins could be transferred in vivo to deficient cells following transfusions given to 6 patients with PNH. All patients were group A1 blood type. Each was given transfusions of 3 U of compatible, washed group O blood. Patient group A1 cells were distinguished from the transfused group O cells by flow cytometry and staining with a labeled lectin, Dolichos biflorus, which specifically binds to group A1 erythrocytes. Increased surface CD59 was measured on recipient red cells and granulocytes 1, 3, and 7 days following transfusion in all 6 patients. Our data suggest a potential therapeutic role for GPI-anchored protein transfer for severe PNH.
Imprint of human cytomegalovirus infection on the NK cell receptor repertoire
Authors: Gumá Mónica , Angulo Ana , Vilches Carlos , Gómez-Lozano Natalia , Malats Núria , López-Botet Miguel
Published: August 2004

Expression of the activating CD94/NKG2C killer lectin-like receptor (KLR) specific for HLA-E was analyzed in peripheral blood lymphocytes (PBLs) from healthy adult blood donors; the expression of other natural killer (NK) cell receptors (ie, CD94/NKG2A, KIR, CD85j, CD161, NKp46, NKp30, and NKG2D) was also studied. Human cytomegalovirus (HCMV) infection as well as the HLA-E and killer immunoglobulin-like receptor (KIR) genotypes were considered as potentially relevant variables associated with CD94/NKG2C expression. The proportion of NKG2C+ lymphocytes varied within a wide range (<0.1% to 22.1%), and a significant correlation (r = 0.83; P < .001) between NKG2C+ NK and T cells was noticed. The HLA-E genotype and the number of activating KIR genes of the donors were not significantly related to the percentage of NKG2C+ lymphocytes. By contrast, a positive serology for HCMV, but not for other herpesviruses (ie, Epstein-Barr and herpes simplex), turned out to be strongly associated (P < .001) with increased proportions of NKG2C+ NK and T cells. Remarkably, the CD94/NKG2C+ population expressed lower levels of natural cytotoxicity receptors (NCRs) (ie, NKp30, NKp46) and included higher proportions of KIR+ and CD85j+ cells than CD94/NKG2A+ cells. Altogether, these data support that HCMV infection selectively shapes the natural killer cell receptor (NKR) repertoire of NK and T cells from healthy carrier individuals.
PU.1 is a suppressor of myeloid leukemia, inactivated in mice by gene deletion and mutation of its DNA binding domain
Authors: Cook Wendy D. , McCaw Benjamin J. , Herring Christopher , John Deborah L. , Foote Simon J. , Nutt Stephen L. , Adams Jerry M.
Published: August 2004

In most myeloid leukemias induced in mice by γ-radiation, one copy of chromosome 2 has suffered a deletion. To search for a potential tumor suppressor gene in that region, we have delineated the deletions in a panel of these tumors. A commonly deleted region of 2 megabase pairs (Mbp) includes the gene encoding the PU.1 transcription factor, a powerful inducer of granulocytic/monocytic differentiation. Significantly, in 87% of these tumors the remaining PU.1 allele exhibited point mutations in the PU.1 DNA binding domain. Surprisingly, 86% of these mutations altered a single CpG, implicating deamination of deoxycytidine, a common mutational mechanism, as the origin of this lesion. The “hot spot” resides in the codon for a contact residue essential for DNA binding by PU.1. In keeping with a tumor suppressor role for PU.1, enforced expression of wild-type PU.1 in the promyelocytic leukemia cells inhibited their clonogenic growth, induced monocytic differentiation, and elicited apoptosis. The mutant PU.1 found in tumors retained only minimal growth suppressive function. The results suggest that PU.1 normally suppresses development of myeloid leukemia by promoting differentiation and that the combination of gene deletion and a point mutation that impairs its ability to bind DNA is particularly leukemogenic.
Linear fuzzy gene network models obtained from microarray data by exhaustive search
Authors: Sokhansanj Bahrad A , Fitch Patrick J , Quong Judy N , Quong Andrew A
Published: August 2004

Background

Recent technological advances in high-throughput data collection allow for experimental study of increasingly complex systems on the scale of the whole cellular genome and proteome. Gene network models are needed to interpret the resulting large and complex data sets. Rationally designed perturbations (e.g., gene knock-outs) can be used to iteratively refine hypothetical models, suggesting an approach for high-throughput biological system analysis. We introduce an approach to gene network modeling based on a scalable linear variant of fuzzy logic: a framework with greater resolution than Boolean logic models, but which, while still semi-quantitative, does not require the precise parameter measurement needed for chemical kinetics-based modeling.

Results

We demonstrated our approach with exhaustive search for fuzzy gene interaction models that best fit transcription measurements by microarray of twelve selected genes regulating the yeast cell cycle. Applying an efficient, universally applicable data normalization and fuzzification scheme, the search converged to a small number of models that individually predict experimental data within an error tolerance. Because only gene transcription levels are used to develop the models, they include both direct and indirect regulation of genes.

Conclusion

Biological relationships in the best-fitting fuzzy gene network models successfully recover direct and indirect interactions predicted from previous knowledge to result in transcriptional correlation. Fuzzy models fit on one yeast cell cycle data set robustly predict another experimental data set for the same system. Linear fuzzy gene networks and exhaustive rule search are the first steps towards a framework for an integrated modeling and experiment approach to high-throughput "reverse engineering" of complex biological systems.
MPSS profiling of human embryonic stem cells
Authors: Brandenberger Ralph , Khrebtukova Irina , Thies R Scott , Miura Takumi , Jingli Cai , Puri Raj , Vasicek Tom , Lebkowski Jane , Rao Mahendra
Published: August 2004

Background

Pooled human embryonic stem cells (hESC) cell lines were profiled to obtain a comprehensive list of genes common to undifferentiated human embryonic stem cells.

Results

Pooled hESC lines were profiled to obtain a comprehensive list of genes common to human ES cells. Massively parallel signature sequencing (MPSS) of approximately three million signature tags (signatures) identified close to eleven thousand unique transcripts, of which approximately 25% were uncharacterised or novel genes. Expression of previously identified ES cell markers was confirmed and multiple genes not known to be expressed by ES cells were identified by comparing with public SAGE databases, EST libraries and parallel analysis by microarray and RT-PCR. Chromosomal mapping of expressed genes failed to identify major hotspots and confirmed expression of genes that map to the X and Y chromosome. Comparison with published data sets confirmed the validity of the analysis and the depth and power of MPSS.

Conclusions

Overall, our analysis provides a molecular signature of genes expressed by undifferentiated ES cells that can be used to monitor the state of ES cells isolated by different laboratories using independent methods and maintained under differing culture conditions
From biomedicine to natural history research: EST resources for ambystomatid salamanders
Authors: Putta Srikrishna , Smith Jeramiah J , Walker John A , Rondet Mathieu , Weisrock David W , Monaghan James , Samuels Amy K , Kump Kevin , King David C , Maness Nicholas J , Habermann Bianca , Tanaka Elly , Bryant Susan V , Gardiner David M , Parichy David M , Voss S Randal
Published: August 2004

Background

Establishing genomic resources for closely related species will provide comparative insights that are crucial for understanding diversity and variability at multiple levels of biological organization. We developed ESTs for Mexican axolotl (Ambystoma mexicanum) and Eastern tiger salamander (A. tigrinum tigrinum), species with deep and diverse research histories.

Results

Approximately 40,000 quality cDNA sequences were isolated for these species from various tissues, including regenerating limb and tail. These sequences and an existing set of 16,030 cDNA sequences for A. mexicanum were processed to yield 35,413 and 20,599 high quality ESTs for A. mexicanum and A. t. tigrinum, respectively. Because the A. t. tigrinum ESTs were obtained primarily from a normalized library, an approximately equal number of contigs were obtained for each species, with 21,091 unique contigs identified overall. The 10,592 contigs that showed significant similarity to sequences from the human RefSeq database reflected a diverse array of molecular functions and biological processes, with many corresponding to genes expressed during spinal cord injury in rat and fin regeneration in zebrafish. To demonstrate the utility of these EST resources, we searched databases to identify probes for regeneration research, characterized intra- and interspecific nucleotide polymorphism, saturated a human – Ambystoma synteny group with marker loci, and extended PCR primer sets designed for A. mexicanum / A. t. tigrinum orthologues to a related tiger salamander species.

Conclusions

Our study highlights the value of developing resources in traditional model systems where the likelihood of information transfer to multiple, closely related taxa is high, thus simultaneously enabling both laboratory and natural history research.
Explaining computation of predictive values: 2 × 2 table versus frequency tree. A randomized controlled trial [ISRCTN74278823]
Authors: Steckelberg Anke , Balgenorth Andrea , Berger Jürgen , Mühlhauser Ingrid
Published: August 2004

Background

Involving patients in decision making on diagnostic procedures requires a basic level of statistical thinking. However, innumeracy is prevalent even among physicians. In medical teaching the 2 × 2 table is widely used as a visual help for computations whereas in psychology the frequency tree is favoured. We assumed that the 2 × 2 table is more suitable to support computations of predictive values.

Methods

184 students without prior statistical training were randomised either to a step-by-step self-learning tutorial using the 2 × 2 table (n = 94) or the frequency tree (n = 90). During the training session students were instructed by two sample tasks and a total of five positive predictive values had to be computed. During a follow-up session 4 weeks later participants had to compute 5 different tasks of comparable degree of difficulty without having the tutorial instructions at their disposal. The primary outcome was the correct solution of the tasks.

Results

There were no statistically significant differences between the two groups. About 58% achieved correct solutions in 4–5 tasks following the training session and 26% in the follow-up examination.

Conclusions

These findings do not support the hypothesis that the 2 × 2 table is more valuable to facilitate the calculation of positive predictive values than the frequency tree.
Electroconvulsive therapy and determination of cerebral dominance
Authors: Dragovic Milan , Allet Lindsay , Janca Aleksandar
Published: August 2004

Electroconvulsive therapy (ECT) often results in a number of short- and long-time side effects including memory impairment for past and current events, which can last for several months after ECT treatment. It has been suggested that unilateral ECT (uECT) with electrodes placed over the non-dominant (typically right) hemisphere significantly reduces side effects, especially memory disturbances. It is important to note that cerebral dominance equates to speech dominance and avoiding this area of the brain also reduces speech dysfunction after ECT. Traditionally, the routine clinical determination of cerebral dominance has been through the assessment of hand, foot and eye dominance, which is an easy and inexpensive approach that, however, does not ensure accuracy. This review of literature on different methods and techniques for determination of cerebral dominance and provides evidence that functional transcranial Doppler sonography (fTCD) represents a valid and safe alternative to invasive techniques for identifying speech lateralisation. It can be concluded that fTCD, notwithstanding its costs, could be used as a standard procedure prior to uECT treatment to determine cerebral dominance, thereby further reducing cognitive side-effects of ECT and possibly making it more acceptable to both patients and clinicians.
The new reconstruction technique in the treatment of the skin cancers located on the eyelid: Posterior temporalis fascia composite graft
Authors: Copcu Eray , Sivrioglu Nazan
Published: August 2004

Background

Difficulty of reconstruction of the eyelids arises from the need to reconstruct different supporting and covering structures in a single operation. Defects in the anterior lamella of the eyelids can be readily repaired with skin grafts or flaps but posterior lamellar reconstruction needs more complex applications.

Methods

We performed posterior lamellar eyelid reconstruction with posterior parts of the temporalis fascia, since their anatomical and histological features are very similar to the defects. Nine patients with skin tumors located on the periorbital region were treated with local skin flaps and deep layer of the temporalis fascia.

Results

Grafts were harvested very easily. There was no complication related with graft or donor site. Biopsy was performed in three cases and normal conjunctival elements were seen. Functional and acceptable aesthetically results were achieved in all patients.

Conclusion

Ideal reconstructive material for replacement of the posterior lamina is still lacking. Tarsal reconstruction can be made with deep temporalis fascia with success since the thickness of the both tissues are very similar and also since the loose areolar layer of the temporalis fascia is very thin and highly vascularized, this layer can be used in reconstruction of the conjunctiva. According to our knowledge this is the first report of using of the posterior part of temporalis fascia as a composite graft in the literature.
Hürthle cell carcinoma: diagnostic and therapeutic implications
Authors: Hanief Mohamed R , Igali Laszlo , Grama Dimitrie
Published: August 2004

Background

Hürthle cell carcinoma is a variant of follicular cell carcinoma of thyroid. It may present as a low-grade tumour or as a more aggressive type. Prognosis depends upon the age of the patient, tumour size, extent of invasion and initial nodal or distant metastasis.

Patient and methods

The case of Hürthle cell carcinoma is reported in a 79-year-old man who presented with a rapidly increasing lump on the left side of his neck, having had a right hemithyroidectomy for colloid goitre 24-years-ago. Fine needle aspiration cytology confirmed the presence of Hürthle cells, raising the possibility of a Hürthle cell neoplasm. The patient underwent staging and surgery. Histology showed Hürthle cell carcinoma and the patient underwent adjuvant therapy. The literature on Hürthle cell neoplasms is reviewed.

Conclusions

Fine needle aspiration cytology may recognise Hürthle cell lesion but final diagnosis of carcinoma depends upon histological confirmation of vascular or capsular invasion. Staging and surgery in Hürthle cell carcinoma are similar to follicular carcinoma of thyroid with favourable outcome despite the controversy regarding the histological classification and adjuvant therapy. Elderly patients with Hürthle cell carcinoma need to be made aware of their poorer prognosis and should be offered more radical treatment.
A first-draft human protein-interaction map
Authors: Lehner Ben , Fraser Andrew G
Published: August 2004

Background

Protein-interaction maps are powerful tools for suggesting the cellular functions of genes. Although large-scale protein-interaction maps have been generated for several invertebrate species, projects of a similar scale have not yet been described for any mammal. Because many physical interactions are conserved between species, it should be possible to infer information about human protein interactions (and hence protein function) using model organism protein-interaction datasets.

Results

Here we describe a network of over 70,000 predicted physical interactions between around 6,200 human proteins generated using the data from lower eukaryotic protein-interaction maps. The physiological relevance of this network is supported by its ability to preferentially connect human proteins that share the same functional annotations, and we show how the network can be used to successfully predict the functions of human proteins. We find that combining interaction datasets from a single organism (but generated using independent assays) and combining interaction datasets from two organisms (but generated using the same assay) are both very effective ways of further improving the accuracy of protein-interaction maps.

Conclusions

The complete network predicts interactions for a third of human genes, including 448 human disease genes and 1,482 genes of unknown function, and so provides a rich framework for biomedical research.
An Ambystoma mexicanumEST sequencing project: analysis of 17,352 expressed sequence tags from embryonic and regenerating blastema cDNA libraries
Authors: Habermann Bianca , Bebin Anne-Gaelle , Herklotz Stephan , Volkmer Michael , Eckelt Kay , Pehlke Kerstin , Epperlein Hans Henning , Schackert Hans Konrad , Wiebe Glenis , Tanaka Elly M
Published: August 2004

Background

The ambystomatid salamander, Ambystoma mexicanum (axolotl), is an important model organism in evolutionary and regeneration research but relatively little sequence information has so far been available. This is a major limitation for molecular studies on caudate development, regeneration and evolution. To address this lack of sequence information we have generated an expressed sequence tag (EST) database for A. mexicanum.

Results

Two cDNA libraries, one made from stage 18-22 embryos and the other from day-6 regenerating tail blastemas, generated 17,352 sequences. From the sequenced ESTs, 6,377 contigs were assembled that probably represent 25% of the expressed genes in this organism. Sequence comparison revealed significant homology to entries in the NCBI non-redundant database. Further examination of this gene set revealed the presence of genes involved in important cell and developmental processes, including cell proliferation, cell differentiation and cell-cell communication. On the basis of these data, we have performed phylogenetic analysis of key cell-cycle regulators. Interestingly, while cell-cycle proteins such as the cyclin B family display expected evolutionary relationships, the cyclin-dependent kinase inhibitor 1 gene family shows an unusual evolutionary behavior among the amphibians.

Conclusions

Our analysis reveals the importance of a comprehensive sequence set from a representative of the Caudata and illustrates that the EST sequence database is a rich source of molecular, developmental and regeneration studies. To aid in data mining, the ESTs have been organized into an easily searchable database that is freely available online.
Microscopy Images as Interactive Tools in Cell Modeling and Cell Biology Education
Authors: Araújo-Jorge Tania C. , Cardona Tania S. , Mendes Cláudia L.S. , Henriques-Pons Andrea , Meirelles Rosane M.S. , Coutinho Cláudia M.L.M. , Aguiar Luiz Edmundo V. , de Nazareth L. Meirelles Maria , de Castro Solange L. , Barbosa Helene S. , Luz Mauricio R.M.P.
Published: August 2004

The advent of genomics, proteomics, and microarray technology has brought much excitement to science, both in teaching and in learning. The public is eager to know about the processes of life. In the present context of the explosive growth of scientific information, a major challenge of modern cell biology is to popularize basic concepts of structures and functions of living cells, to introduce people to the scientific method, to stimulate inquiry, and to analyze and synthesize concepts and paradigms. In this essay we present our experience in mixing science and education in Brazil. For two decades we have developed activities for the science education of teachers and undergraduate students, using microscopy images generated by our work as cell biologists. We describe open-air outreach education activities, games, cell modeling, and other practical and innovative activities presented in public squares and favelas. Especially in developing countries, science education is important, since it may lead to an improvement in quality of life while advancing understanding of traditional scientific ideas. We show that teaching and research can be mutually beneficial rather than competing pursuits in advancing these goals.
Using the principles of Exploratory Practice to guide group work in an extensive reading class in China
Authors: Zhang Ruwen
Published: August 2004

Exploratory Practice emphasizes integrating research into pedagogy, and attaches great importance to the quality of life in the classroom. It suggests that we work primarily to understand language classroom life, to bring people together, and to develop students’ language competency in a harmonious atmosphere.By putting EP principles into my teaching practice, I explore ways of solving a problem I experienced in teaching English extensive reading to English majors in a Chinese University.
Breathing techniques in patients with chronic obstructive pulmonary disease (COPD)
Authors: Gosselink R
Published: August 2004

Background:Breathing techniques are included in the rehabilitation program of patients with chronic obstructive pulmonary disease (COPD). The efficacy of breathing techniques aiming at improving symptoms of dyspnea and eliciting physiological effects is discussed in this paper. In patients with COPD, breathing techniques aim to relieve symptoms and ameliorate adverse physiological effects by: 1) increasing strength and endurance of the respiratory muscles; 2) optimizing the pattern of thoracoabdominal motion; and 3) reducing dynamic hyperinflation of the rib cage and improving gas exchange. Evidence exists to support the effectiveness of pursed lips breathing, forward leaning position, active expiration and inspiratory muscle training, but not for diaphragmatic breathing. Careful patient selection, proper and repeated instruction and control of the techniques, and assessment of the effects are necessary. Despite the evidence that breathing techniques are effective, several problems need to be resolved. The limited evidence for the transfer of the effects of breathing techniques during resting conditions to exercise conditions raises several questions. Do breathing techniques have to be practiced during activities of daily living?
Chronic bronchitis: should it worry us?
Authors: Vestbo J
Published: August 2004

Background: Chronic bronchitis (CB) has been studied using standardized questionnaires for decades. From being the key element in the ‘British hypothesis’ chronic bronchitis was reduced to being an innocent disorder in the 1980s. However, there is now good evidence that chronic bronchitis is associated with an increased risk from both overall and chronic obstructive pulmonary disease (COPD) specific mortality. Presumably through increasing the frequency of lower respiratory tract infections chronic bronchitis is associated with excess decline in lung function, hospital admission and other disease specific outcomes. The prevalence of chronic bronchitis increases with increasing age and the burden associated with chronic bronchitis in this growing proportion of the population is large. Vital prognosis in the elderly is affected by CB and this condition presumably deserves more attention from the medical profession.
Prescribing practice for intermittent oxygen therapy: a GP survey
Authors: O'Neill B , Bradley J M , McKevitt A M , Heaney L , Riley M , McGovem V , MacMahon J
Published: August 2004

Introduction:UK figures show that the prescription of home oxygen cylinders for intermittent use is substantial. Aim: To examine GP assessment criteria and prescribing practice for intermittent oxygen therapy in patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in Northern Ireland. Methods:A postal questionnaire was sent to all GPs (n = 534) in two health boards who had prescribed cylinder oxygen in a six month period prior to the study. The questionnaire was piloted to establish reliability and validity. Results:Completed questionnaires were returned by 52% (280/534) of GPs. GPs ‘most frequently’ used advice from hospital specialists [82% (230/280)] to determine the need for intermittent oxygen. Criteria such as breathlessness score on exercise (e.g., BORG), oximetry on exercise, local guidelines or national guidelines were used less frequently or never. Conclusions:Most patients are likely to have been prescribed intermittent oxygen without any objective assessment. Implementation of evidence-based guidelines and a formal oxygen assessment service, would rationalize the use of intermittent oxygen therapy and enable better targeting of this expensive resource.
Crosscultural communication in those with airway diseases
Authors: Carl J , Partridge M R
Published: August 2004

Transcultural consultations are becoming commonplace. Such consultations arise because patients from ethnic groups consult doctors, but also because patients consult doctors from other ethnic backgrounds. Such consultations require a cultural awareness and sensitivity which may be particularly necessary when concerning those with respiratory illnesses which are often long-term and about which there may be considerable stigma. The prevalence of respiratory disease can vary between ethnic groups, most noticeably in tuberculosis and smoking; and in diseases such as asthma, health service usage and treatment can vary significantly with ethnicity. Some of this may represent cultural, rather than disease specific differences. Good communication is essential throughout medical practice, but in transcultural consultations it is especially important that the doctor pays appropriate attention to likely patient beliefs and approaches to shared decision making. Usual negotiation regarding goals and outcomes first requires the clinician to understand how a patient's understanding of illness may vary from a traditional western scientific approach. Special attention needs to be paid to the optimal way of using interpreters and more time is often needed for crosscultural consultations. Specific training is necessary for health practitioners to enable them to acquire the skills for crosscultural care and this involves learning about other cultures and an appreciation of how a change in attitude often needs to be incorporated into the clinical approach. Acquiring these skills and understandings to facilitate optimal transcultural consultation enables transfer of these skills to other similar clinical scenarios such as the approach to those with disability. The global burden of long-term respiratory disease, both infectious and noncommunicable, coupled with increased migration and geographical mobility means that a successful crosscultural approach is now a priority area for attention.
Phase I Trial of Preoperative Doxorubicin-Based Concurrent Chemoradiation and Surgical Resection for Localized Extremity and Body Wall Soft Tissue Sarcomas
Authors: Pisters Peter W.T. , Patel Shreyaskumar R. , Prieto Victor G. , Thall Peter F. , Lewis Valerae O. , Feig Barry W. , Hunt Kelly K. , Yasko Alan W. , Lin Patrick P. , Jacobson Marc G. , Burgess Michael A. , Pollock Raphael E. , Zagars Gunar K. , Benjamin Robert S. , Ballo Matthew T.
Published: August 2004

Purpose

The primary objective of this phase I trial was to define the maximum-tolerated dose of continuous-infusion doxorubicin administered with standard preoperative radiation for patients with localized, potentially resectable soft tissue sarcomas of the extremities or body wall.

Patients and Methods

Twenty-seven patients with radiographically resectable intermediate- or high-grade soft tissue sarcomas were treated. Preoperative external-beam radiation was administered in 25 2-Gy fractions (total dose, 50 Gy). Concurrent continuous-infusion doxorubicin was administered by an initial bolus (4 mg/m2) and subsequent 4-day continuous infusion (12.5, 15.0, 17.5, or 20.0 mg/m2/wk). Radiographic restaging was performed 4 to 7 weeks after chemoradiation, and patients with localized disease underwent surgical resection.

Results

Chemoradiation was completed as an outpatient procedure in 25 patients (93%). The maximum-tolerated dose of continuous-infusion doxorubicin combined with standard preoperative radiation was 17.5 mg/m2/wk; at this dose level, seven (30%) of 23 patients had grade 3 dermatologic toxicity. Macroscopically complete resection (R0 or R1) was performed in all 26 patients who underwent surgery. Among 22 patients who were treated with doxorubicin 17.5/mg/m2/wk with concurrent radiation and subsequent surgery, 11 patients (50%) had 90% or greater tumor necrosis, including two patients who had complete pathologic responses.

Conclusion

Preoperative doxorubicin-based chemoradiation appears safe and feasible. The maximum-tolerated dose of continuous-infusion doxorubicin with standard preoperative radiation was 17.5 mg/m2/wk. Pathologic response rates with this regimen are encouraging.
Role of the Dependence Receptor DCC in Colorectal Cancer Pathogenesis
Authors: Mehlen Patrick , Fearon Eric R.
Published: August 2004

More than a decade ago, the DCC (deleted in colorectal cancer) gene was proposed as a putative tumor suppressor gene. Data supporting this proposal included observations that one DCC allele was deleted in roughly 70% of colorectal cancers, some cancers had somatic mutations of the DCC gene, and DCC expression was often reduced or absent in colorectal cancer tissues and cell lines. Despite subsequent studies which have supported DCC's potential role as a tumor suppressor gene, the rarity of point mutations identified in DCC coding sequences, the lack of a tumor predisposition phenotype in mice heterozygous for DCC inactivating mutations, and the presence of other known and candidate tumor suppressor genes on chromosome 18q have raised questions about DCC's candidacy. Following its initial characterization, the DCC protein was identified as a transmembrane receptor for netrins, key factors in axon guidance in the developing nervous system. At first glance, the established role of DCC and netrin-1 during organization of the spinal cord could be viewed as a further challenge to the position that DCC inactivation might play a significant role in tumorigenesis. However, recent observations on DCC's functions in intracellular signaling have renewed interest in the potential contribution of DCC inactivation to cancer. In particular, data indicate that, when engaged by netrin ligands, DCC may activate downstream signaling pathways. Moreover, in settings where netrin is absent or at low levels, DCC can promote apoptosis. Here, we review DCC's candidacy as a tumor suppressor gene, with an emphasis on how recent molecular analyses of DCC have offered support for the notion that DCC may function as a tumor suppressor gene.
Population Variations in the Initial Treatment of Non–Small-Cell Lung Cancer
Authors: Potosky Arnold L. , Saxman Scott , Wallace Robert B. , Lynch Charles F.
Published: August 2004

Purpose

Dissemination of recommended therapies for non–small-cell lung cancer (NSCLC) have not been described comprehensively. We report the patterns of initial therapy focusing on the investigation of differences in receipt of recommended therapies according to multiple clinical and nonclinical patient characteristics.

Methods

A population-based random sample of newly diagnosed NSCLC patients diagnosed in 10 separate geographic areas was collected in 1996 (n = 898). Data were obtained from medical records. Multiple logistic regression was used to assess the use of recommended therapies.

Results

Overall, 52% of NSCLC patients received recommended therapy. Approximately 69%, 48%, and 41% of patients with stages I and II, III, or IV NSCLC received recommended therapy, respectively. For all stages combined, the use of recommended therapy was significantly inversely associated with age and stage at diagnosis. Recommended therapy also was more common in white versus black patients, and in married versus single patients. Stage-specific analyses revealed a significant decline in the use of recommended surgery with increasing age at diagnosis for early-stage NSCLC only, and a significantly lower use of recommended therapy (primarily chemoradiotherapy) for stage III black and Hispanic patients compared with white patients.

Conclusion

The overall use of recommended therapies for NSCLC is low. Large variations exist in the use of such therapies according to age, race or ethnicity, and marital status. Research combining medical record reviews with other sources of data is needed to better understand the contributions of both patient preferences and physician judgment to these treatment variations.
Health-Related Quality of Life Parameters As Prognostic Factors in a Nonmetastatic Breast Cancer Population: An International Multicenter Study
Authors: Efficace Fabio , Therasse Patrick , Piccart Martine J. , Coens Corneel , Van Steen Kristel , Welnicka-Jaskiewicz Marzena , Cufer Tanja , Dyczka Jaroslaw , Lichinitser Michail , Shepherd Lois , de Haes Hanneke , Sprangers Mirjam A. , Bottomley Andrew
Published: August 2004

Purpose

The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages.

Patients and Methods

The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty.

Results

The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P = .03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis.

Conclusion

Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population.
Expression of Hepatoma-Derived Growth Factor Is a Strong Prognostic Predictor for Patients With Early-Stage Non–Small-Cell Lung Cancer
Authors: Ren Hening , Tang Ximing , Lee J. Jack , Feng Lei , Everett Allen D. , Hong Waun Ki , Khuri Fadlo R. , Mao Li
Published: August 2004

Purpose

Hepatoma-derived growth factor (HDGF), which is unrelated to hepatocyte growth factor, can stimulate DNA synthesis and cell proliferation on entering the nucleus. We hypothesize that HDGF plays an important role in biologic behavior of early-stage non–small-cell lung cancer (NSCLC).

Patients and Methods

Ninety-eight patients with pathologic stage I NSCLC who underwent curative surgery were studied. Immunohistochemistry was used to determine the expression level of HDGF in the tumor specimens. The intensity of the protein staining and percentage of stained tumor cells were used to determine a labeling index. Statistical analyses, all two-sided, were performed to determine the prognostic effect of HDGF expression levels on clinical parameters and outcomes.

Results

The mean ± standard deviation HDGF labeling index in the 98 tumors was 185 ± 41. Patients whose tumors had higher HDGF indexes (≥ 185) had a significantly poorer probability of overall survival at 5 years after surgery than did those with lower HDGF indexes (0.26 v 0.82; P < .0001). Similarly, the 5-year disease-specific and disease-free survival probabilities were lower in those with higher HDGF indexes (0.42 v 0.92, and 0.34 v 0.71; P < .0001 and P = .0008; respectively). Multivariate analysis indicated that HDGF level was an independent predictor of overall, disease-specific, and disease-free survivals.

Conclusion

Overexpression of HDGF is common in early-stage NSCLC. The expression level in tumor cells is strongly correlated with poor overall, disease-specific, and disease-free survivals, suggesting HDGF may be a powerful prognostic marker for patients with early-stage NSCLC.
Randomized Trial of a Shared Decision-Making Intervention Consisting of Trade-Offs and Individualized Treatment Information for BRCA1/2 Mutation Carriers
Authors: van Roosmalen M.S. , Stalmeier P.F.M. , Verhoef L.C.G. , Hoekstra-Weebers J.E.H.M. , Oosterwijk J.C. , Hoogerbrugge N. , Moog U. , van Daal W.A.J.
Published: August 2004

Purpose

To evaluate a shared decision-making intervention (SDMI) for BRCA1/2 mutation carriers who have to make a choice between screening and prophylactic surgery for breasts and/or ovaries.

Patients and Methods

The SDMI consisted of two value assessment sessions, using the time trade-off method, followed by individualized treatment information based on (quality-adjusted) life expectancy. After the baseline assessment (2 weeks after a positive DNA test result), women were randomly assigned to the SDMI group (n = 44), receiving the SDMI 2 months after the test result, or to the control group (n = 44). The short- and long-term effects, 3 and 9 months after the test result, were assessed using questionnaires. Data were collected on well-being, treatment choice, and decision-related outcomes.

Results

In the short term, the SDMI had no effect. In the long term, with respect to well-being, patients in the SDMI group had less intrusive thoughts (P = .05) and better general health (P = .01) and tended to be less depressed (P = .07). With respect to decision-related outcomes for the breasts, the SDMI group held stronger preferences (P = .02) and agreed more strongly to having weighed the pros and cons (P = .01). No effect was found on treatment choice. In the long term, interaction effects between the SDMI and cancer history were found. The SDMI showed an overall beneficial effect for unaffected women, whereas affected women tended to experience detrimental effects.

Conclusion

We conclude that the SDMI improved decision making in unaffected BRCA1/2 mutation carriers. Supporting decision making in a systematic way using trade-offs is beneficial for these women.
Breast Cancer With Synchronous Metastases: Trends in Survival During a 14-Year Period
Authors: Andre Fabrice , Slimane Khemaies , Bachelot Thomas , Dunant Arianne , Namer Moise , Barrelier Alain , Kabbaj Omar , Spano Jean Philippe , Marsiglia Hugo , Rouzier Roman , Delaloge Suzette , Spielmann Marc
Published: August 2004

Purpose

Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis.

Patients and Methods

A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by χ2 test, log-rank test, and Cox regression analysis.

Results

Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P < .001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P < .001).

Conclusion

The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.