bluuebunny/crossref_metadata_2025 huggingface dataset:
Aberrant methylation in the promoter region of the reduced folate carrier gene is a potential mechanism of resistance to methotrexate in primary central nervous system lymphomas
Authors: Ferreri Andrés J. M. , Dell'Oro Stefania , Capello Daniela , Ponzoni Maurilio , Iuzzolino Paolo , Rossi Davide , Pasini Felice , Ambrosetti Achille , Orvieto Enrico , Ferrarese Fabio , Arrigoni Gianluigi , Foppoli Marco , Reni Michele , Gaidano Gianluca
Published: August 2004

We investigated the prevalence and prognostic role of CpG island methylation of the reduced folate carrier (RFC) gene promoter region in primary central nervous system lymphoma (PCNSL) in immunocompetent patients. Genomic DNA from 40 PCNSL was used for methylation‐specific polymerase chain reaction and bisulphite genomic sequencing of the RFC promoter region. Human immunodeficiency virus‐negative systemic diffuse large B‐cell lymphomas (DLBCL) were used as controls (n = 50). The impact on outcome of RFC promoter methylation was assessed in 37 PCNSL patients treated with high‐dose methotrexate (HD‐MTX)‐based chemotherapy ± radiotherapy. RFC promoter methylation occurred in 12 of 40 (30%) PCNSL and in four of 50 (8%) DLBCL (P = 0·01). Of 37 PCNSL treated with HD‐MTX‐based chemotherapy, methylation occurred in nine cases (24%, M‐PCNSL), while 28 cases (76%, U‐PCNSL) were negative. Three M‐PCNSL (33%) and 15 U‐PCNSL (54%) achieved complete remission (CR) after primary chemotherapy. Logistic regression confirmed the independent association between CR rate and International Extranodal Lymphoma Study Group score (P = 0·03), RFC promoter methylation (P = 0·07) and use of cytarabine (P = 0·08). The 3‐year failure‐free survival (FFS) and overall survival for M‐PCNSL and U‐PCNSL was 0% vs. 31 ± 9% (P = 0·34) and 0% vs. 31 ± 9% (P = 0·35) respectively. This is the first study to assess the methylation status of the RFC promoter in human tumour samples. RFC methylation is more common in PCNSL compared with systemic DLBCL, and is associated with a lower CR rate to HD‐MTX‐based chemotherapy. If confirmed in prospective trials on PCNSL treated with HD‐MTX alone, these data may suggest the necessity for alternative strategies in M‐PCNSL considering the increased risk of MTX resistance by tumour cells.
Post‐transplantation tumour load in bone marrow, as assessed by quantitative ASO‐PCR, is a prognostic parameter in multiple myeloma
Authors: Bakkus Marleen H. C. , Bouko Yasmina , Samson Diana , Apperley Jane F. , Thielemans Kris , Camp Benjamin Van , Benner Axel , Goldschmidt Hartmut , Moos Marion , Cremer Friedrich W.
Published: August 2004

High‐dose therapy (HDT) and autologous transplantation prolongs remission duration and survival in multiple myeloma (MM), but relapse still occurs at a median of 2 years post‐HDT. In order to investigate whether the number of residual tumour cells in the bone marrow (BM) after transplantation can predict the duration of response, a quantitative allele‐specific oligonucleotide polymerase chain reaction (qASO‐PCR) assay was used to measure tumour load in BM at 3–6 months post‐HDT in 67 patients. The method of maximally selected log‐rank statistics was used to test for the existence of a cut‐off value in the BM tumour load data set. A cut‐off value with respect to progression‐free survival (PFS) was identified (P = 0·001). The estimated threshold for placing patients into a ‘good’ or ‘bad’ prognostic group was 0·015% (n = 22 and 38 respectively) with a median PFS of 64 months vs. 16. Multivariate analysis showed grouping by PCR result to be an independent prognostic factor for PFS (estimated hazard ratio after shrinkage, 3·91). This study identifies for the first time a threshold of the post‐HDT tumour load with prognostic significance for PFS in MM. Quantitative molecular assessment thus may help to identify those patients who are in need of further treatment early after autologous transplantation.
Involvement of nurses in physician‐assisted dying
Authors: Bilsen Johan J.R. , Vander Stichele Robert H. , Mortier Freddy , Deliens Luc
Published: August 2004

Background.  Death in modern societies is often preceded by medical end‐of‐life decisions. Empirical research on these end‐of‐life decisions focuses predominantly on the physicians’ role. Little is known about the role of other health care workers, especially that of nurses.

Aim.  This paper reports the findings of a study that investigated how often nurses are consulted by physicians in the decision‐making process preceding end‐of‐life decisions and how often nurses participate in administering lethal drugs in end‐of‐life decisions.

Method.  Data were collected within a nationwide cross‐sectional retrospective death certificate study in Flanders, the Dutch‐speaking part of Belgium. We selected 3999 deaths, a 20% random sample of all those occurring during the first 4 months of 1998. Anonymous questionnaires were mailed to the physicians who signed the death certificates. Several questions concerned the involvement of nurses in end‐of‐life decisions.

Results.  We received 1925 valid questionnaires. For all reported end‐of‐life decisions (39·3% of all deaths in Flanders), physicians provided information about the involvement of nurses. Physicians consulted at least one nurse in 52% of end‐of‐life decisions cases occurring in institutions, compared with 21·4% of such cases at home. Nurses administered lethal drugs in 58·8% of euthanasia cases occurring in institutions and in 17·2% at home. For cases in which life was ended without the patient's explicit request because, predominantly, they were too ill to do so, these percentages were respectively 82·7% and 25·2%. In institutions, nurses mostly administered drugs without the attendance of a physician who had prescribed the drugs.

Conclusions.  Nurses in Belgium are largely involved in administering lethal drugs in end‐of‐life decisions, while their participation in the decision‐making process is rather limited. To guarantee prudent practice in end‐of‐life decisions, we need clear guidelines, professionally supported and legally controlled, for the assignment of duties between physicians and nurses regarding the administration of lethal drugs to reflect current working practice. In addition, we need appropriate binding standards governing mutual communication about all end‐of‐life decisions.
Palliative care nurses’ views on euthanasia
Authors: Verpoort Charlotte , Gastmans Chris , Casterlé Bernadette Dierckx de
Published: August 2004

Background.  In debates on euthanasia legalization in Belgium, the voices of nurses were scarcely heard. Yet studies have shown that nurses are involved in the caring process surrounding euthanasia. Consequently, they are in a position to offer valuable ideas about this problem. For this reason, the views of these nurses are important because of their palliative expertise and their daily confrontation with dying patients.

Aim.  The aim of this paper is to report a study of the views of palliative care nurses about euthanasia.

Methods.  A grounded theory approach was chosen, and interviews were carried out with a convenience sample of 12 palliative care nurses in Flanders (Belgium). The data were collected between December 2001 and April 2002.

Findings.  The majority of the nurses were not a priori for or against euthanasia, and their views were largely dependent on the situation. What counted was the degree of suffering and available palliative options. Depending on the situation, we noted both resistance and acceptance towards euthanasia. The underlying arguments for resistance included respect for life and belief in the capabilities of palliative care; arguments underlying acceptance included the quality of life and respect for patient autonomy. The nurses commented that working in palliative care had a considerable influence on one's opinion about euthanasia.

Conclusion.  In light of the worldwide debate on euthanasia, it is essential to know how nurses, who are confronted with terminally ill patients every day, think about it. Knowledge of these views can also contribute to a realistic and qualified view on euthanasia itself. This can be enlightening to the personal views of caregivers working in a diverse range of care settings.
Use of intuition by nursing students: instrument development and testing
Authors: Smith Anita J. , Thurkettle Mary Ann , Cruz Felicitas A. dela
Published: August 2004

Background.  Intuition has been described as an important type of nursing knowledge and has gained acceptance as a valid way of knowing in clinical nursing. Use of intuition has become one way of explaining professional expertise. Measures of the use of intuition have been developed primarily for experienced nurses, but few measures of intuition use among nursing students exist.

Aim.  The aim of this paper is to describe the development and psychometric testing of an instrument to measure use of intuition by nursing students.

Methods.  Instrument development consisted of concept clarification, item development, and psychometric testing. Intuition was defined as a non‐linear process of knowing perceived through physical awareness, emotional awareness, and/or through physical or spiritual connections. Initial measurement items were derived inductively from the literature and informal interviews with senior nursing students. Seven content experts established a content validity index of 0·86 for the initial 33‐item measure. It was pretested with a sample of 20 senior nursing students prior to its nationwide validation with a random sample of 1000 senior bachelor of science and associate degree nursing students.

Results.  Postal mail data collection resulted in 349 responses (35% response rate). Principal component analysis with orthogonal varimax rotation resulted in seven factors accounting for 66·2% of the variance: physical sensations (28·4%); premonitions (9·7%); spiritual connections (7·7%); reading of cues (6.1%); sensing energy (5·7%); apprehension (4·3%); and reassuring feelings (4%). Eigenvalues ranged from 1 to 7·1 and factor loadings ranged from 0·534 to 0·858. The validation resulted in a revised 25‐item measure that demonstrated an overall Cronbach's alpha of 0·89 and a range of 0·69–0·84 for each factor. The study is limited by the use of a self‐report measure and the attrition in the randomized sample.

Conclusions.  The intuition measure for use with students showed evidence of construct validity and reliability. With further testing, the measure could serve as a stimulus to foster students’ intuitive abilities.
Learning to nurse children: towards a model for nursing students
Authors: Coetzee Minette
Published: August 2004

Background.  As undergraduate nursing students approach their paediatric placement, their anticipation ranges from keen expectation to anxious avoidance. This placement has been described as the most stressful in nursing programmes. While various nurse scholars have attempted to describe the practice and the theory of nursing, it has been the challenge of nurse teachers to weave the theory and practice of nursing together for their students. The nature of this learning is, however, still being explored.

Aim.  This paper reports a study whose aim was to describe, and propose a theoretical understanding of, how nursing students learn to care for children.

Method.  In this grounded theory study, participants were drawn from four consecutive student groups in their third year of a Bachelor of Nursing programme. Data included participant observation, focus groups and student descriptions, from both personal reflective journals and narratives. The qualitative research paradigm and the interlaced, often simultaneous, roles of researcher and teacher defined the design and implementation of the study.

Findings.  Data analysis confirmed the complex nature of students’ learning to care. The relationships that they established with children and others (families, peers, clinical nurses and lecturers) whom they encountered emerged as key in their learning. The social process that was central to student learning was working out how to connect with a child in their care: puzzling out a connection. Each connection with a child contributed to the next and thus to the student's learning. Each connection also contributed to the student's resources, knowledge and experience base, adding to learning by further equipping the student for the next encounter with a child.

Conclusion.  The resulting theory contributes towards understanding the complexity of learning to care for children. The relational nature of learning shown in this work can guide the structuring and evaluation of learning environments in child nursing programmes. The context of interpersonal relationships of students when learning to care for children provides evidence for re‐examining how nurse teachers facilitate and evaluate student learning in child nursing programmes.
Sugar maple (Acer saccharum Marsh.) establishment in boreal forest: results of a transplantation experiment
Authors: Kellman Martin
Published: August 2004

Aim  To evaluate whether seedlings of sugar maple (Acer saccharum Marsh.) can establish beyond the species northern range limit in adjacent boreal forest.

Location  The hardwood–boreal forest transition zone on the north‐east shore of Lake Superior, Ontario, Canada.

Methods  Seed fall of sugar maple was monitored for 5 years in a stand of this species at its northern range limit, and seed from this stand was transplanted to five micro‐habitat types in an adjacent boreal forest. The establishment and survival of sugar maple seedlings there, and in the seed‐source stand, was monitored for the following 7–11 years. Soil‐surface light levels were measured in both forest types.

Results  Most seed fell in the final year of monitoring, when c. 250 seeds m−2 were recorded. First‐year seedling establishment rates in the maple stand, deriving from this mast seed year, was approximately double that deriving from seed transplanted to the boreal forest sites; this is tentatively attributed to seed predator satiation in the maple stand. However, subsequent seedling survivorship in the boreal forest was greater than that in the maple stand, resulting in comparable seedling densities by the end of 6 years. This difference is tentatively attributed to better illumination in the boreal forest sites, and canopy‐opening disturbances appear to be especially facilitative of seedling survival.

Main conclusions  There is no fundamental impediment to sugar maple seedlings establishing in boreal forest communities if climate warming occurs and seed is available. If management intervention is needed to accelerate seed availability in a rapidly warming boreal forest, then diffuse seed application to disturbed boreal forest sites during mast years of local boreal tree species is recommended as the most effective way of avoiding seed predation and increasing seedling survival.
ExoU is a potent intracellular phospholipase
Authors: Sato Hiromi , Frank Dara W.
Published: August 2004

The combination of a large genome encoding metabolic versatility and conserved secreted virulence determinants makes Pseudomonas aeruginosa a model pathogen that can be used to study host–parasite interactions in many eukaryotic hosts. One of the virulence regulons that likely plays a role in the ability of P. aeruginosa to avoid innate immune clearance in mammals is a type III secretion system (TTSS). Upon cellular contact, the P. aeruginosa TTSS is capable of delivering a combination of at least four different effector proteins, exoenzyme S (ExoS), ExoT, ExoU, and ExoY. Two of the four translocated proteins, ExoS and ExoU, are cytotoxic to cells during infection and transfection. The mechanism of cytotoxicity of ExoS is unclear. ExoU, however, has recently been characterized as a member of the phospholipase A family of enzymes, possessing at least phospholipase A2 activity. Similar to ExoS, ExoT and ExoY, ExoU requires either a eukaryotic‐specific modification or cofactor for its activity in vitro. The biologic effects of minimal expression of ExoU in yeast can be visualized by membrane damage to different organelles and fragmentation of the vacuole. In mammalian cells, the direct injection of ExoU causes irreversible damage to cellular membranes and rapid necrotic death. ExoU likely represents a unique enzyme and is the first identified phopholipase virulence factor that is translocated into the cytosol by TTSS.
Respiration metabolism reduces oxidative and acid stress to improve long‐term survival of Lactococcus lactis
Authors: Rezaïki Lahcen , Cesselin Bénédicte , Yamamoto Yuji , Vido Karin , Van West Evelien , Gaudu Philippe , Gruss Alexandra
Published: August 2004

The impact of oxygen on a cell is strongly dependent on its metabolic state: survival in oxygen of free‐living Lactococcus lactis, best known as a fermenting, acidifying bacterium, is generally poor. In contrast, if haem is present, L. lactis uses oxygen to switch from fermentation to respiration metabolism late in growth, resulting in spectacularly improved long‐term survival. Oxygen is thus beneficial rather than detrimental for survival if haem is provided. We examined the effects of respiration on oxygen toxicity by comparing integrity of stationary phase cells after aerated growth without and with added haem. Aeration (no haem) growth caused considerable cellular protein and chromosomal DNA damage, increased spontaneous mutation frequencies and poor survival of recA mutants. These phenotypes were greatly diminished when haem was present, indicating that respiration constitutes an efficient barrier against oxidative stress. Using the green fluorescent protein as an indicator of intracellular oxidation state, we showed that aeration growth provokes significantly greater oxidation than respiration growth. Iron was identified as a main contributor to mortality and DNA degradation in aeration growth. Our results point to two features of respiration growth in lactococci that are responsible for maintaining low oxidative damage: One is a more reduced intracellular state, which is because of efficient oxygen elimination by respiration. The other is a higher pH resulting from the shift from acid‐forming fermentation to respiration metabolism. These results have relevance to other bacteria whose respiration capacity depends on addition of exogenous haem.
Functional domains of the IS1 transposase: analysis in vivo and in vitro
Authors: Ton‐Hoang Bao , Turlan Catherine , Chandler Michael
Published: August 2004

The IS1 bacterial insertion sequence family, considered to be restricted to Enterobacteria, has now been extended to other Eubacteria and to Archaebacteria, reviving interest in its study. To analyse the functional domains of the InsAB′ transposase of IS1A, a representative of this family, we used an in vivo system which measures IS1‐promoted rescue of a temperature‐sensitive pSC101 plasmid by fusion with a pBR322::IS1 derivative. We also describe the partial purification of the IS1 transposase and the development of several in vitro assays for transposase activity. These included a DNA band shift assay, a transposase‐mediated cleavage assay and an integration assay.  Alignments  of  IS  family  members  (http://www‐is.biotoul.fr) not only confirmed the presence of an N‐terminal helix–turn–helix and a C‐terminal DDE motif in InsAB′, but also revealed a putative N‐terminal zinc finger. We have combined the in vitro and in vivo tests to carry out a functional analysis of InsAB′ using a series of site‐directed InsAB′ mutants based on these alignments. The results demonstrate that appropriate mutations in the zinc finger and helix–turn–helix motifs result in loss of binding activity to the ends of IS1 whereas mutations in the DDE domain are affected in subsequent transposition steps but not in end binding.
Redox and antioxidant systems of the malaria parasite Plasmodium falciparum
Authors: Müller Sylke
Published: August 2004

The malaria parasite Plasmodium falciparum is highly adapted to cope with the oxidative stress to which it is exposed during the erythrocytic stages of its life cycle. This includes the defence against oxidative insults arising from the parasite's metabolism of haemoglobin which results in the formation of reactive oxygen species and the release of toxic ferriprotoporphyrin IX. Central to the parasite's defences are superoxide dismutases and thioredoxin‐dependent peroxidases; however, they lack catalase and glutathione peroxidases. The vital importance of the thioredoxin redox cycle (comprising NADPH, thioredoxin reductase and thioredoxin) is emphasized by the confirmation that thioredoxin reductase is essential for the survival of intraerythrocytic P. falciparum. The parasites also contain a fully functional glutathione redox system and the low‐molecular‐weight thiol glutathione is not only an important intracellular thiol redox buffer but also a cofactor for several redox active enzymes such as glutathione S‐transferase and glutaredoxin. Recent findings have shown that in addition to these cytosolic redox systems the parasite also has an important mitochondrial antioxidant defence system and it is suggested that lipoic acid plays a pivotal part in defending the organelle from oxidative damage.
Environmental conditions influencing Sclerotinia sclerotiorum infection and disease development in lettuce
Authors: Young C. S. , Clarkson J. P. , Smith J. A. , Watling M. , Phelps K. , Whipps J. M.
Published: August 2004

The environmental factors that influence infection of lettuce by ascospores of Sclerotinia sclerotiorum, and subsequent disease development, were investigated in controlled environment and field conditions. When lettuce plants were inoculated with a suspension of ascospores in water or with dry ascospores and exposed to a range of wetness durations or relative humidities at different temperatures, all plants developed disease but there was no relationship between leaf wetness duration or humidity and percentage of diseased plants. Ascospores started to germinate on lettuce leaves after 2–4 h of continuous leaf wetness at optimum temperatures of 15–25°C. The rate of development of sclerotinia disease and the final percentage of plants affected after 50 days were greatest at 16–27°C, with disease symptoms first observed 7–9 days after inoculation, and maximum final disease levels of 96%. At lower temperatures, 8–11°C, disease was first observed 20–26 days after inoculation, with maximum final disease levels of 10%. Disease symptoms were always observed first at the stem base. In field‐grown lettuce in Norfolk, 2000 and 2001, inoculated with ascospore suspensions, disease occurred only in lettuce planted in May and June, with a range of 20–49% of plants with disease by 8 weeks after inoculation. In naturally infected field‐grown lettuce in Cheshire, 2000, disease occurred mainly in lettuce planted throughout May, with a maximum of 31% lettuce diseased within one planting, but subsequent plantings had little (≤ 4%) or no disease. Lack of disease in the later plantings in both Norfolk and Cheshire could not be attributed to differences in weather factors.
Genetic variation and covariation for aggressiveness, deoxynivalenol production and fungal colonization among progeny of Gibberella zeae in wheat
Authors: Cumagun C. J. R. , Rabenstein F. , Miedaner T.
Published: August 2004

Gibberella zeae (anamorph Fusarium graminearum) causes head blight of cereals and contaminates grains with mycotoxins such as deoxynivalenol (DON). To determine the correlations among aggressiveness traits, fungal colonization and DON production, 50 progeny from a segregating population of G. zeae were inoculated onto a susceptible winter wheat cultivar in three field environments (year–location combinations). Aggressiveness traits were measured as head‐blight rating and plot yield relative to noninoculated plots. Fungal colonization, measured as Fusarium exoantigen (ExAg) content, and DON production were analysed with two ELISA formats. Disease severity was moderate to high based on head‐blight rating and relative plot yield. Fusarium ExAg content and DON production ranged from 0·26–1·41 units and from 4·18–43·70 mg kg−1, respectively. Significant (P = 0·01) genotypic variation was found for all traits. Heritability for Fusarium ExAg content was rather low because of high progeny–environment interaction and error. DON/Fusarium ExAg ratio did not vary significantly (P > 0·1) among progeny. Correlation between DON production and Fusarium ExAg content across environments was high (r = 0·8, P = 0·01), but no covariation existed between aggressiveness traits and DON/Fusarium ExAg content ratio.
Linkage of Vfa4 in Malus × domestica and Malus floribunda with Vf resistance to the apple scab pathogen Venturia inaequalis
Authors: Afunian M. R. , Goodwin P. H. , Hunter D. M.
Published: August 2004

The Vf locus from Malus floribunda clone 821 is an important source of resistance to apple scab disease caused by Venturia inaequalis, and has been introduced into numerous cultivars of domesticated apple, Malus × domestica. Cloning of the putative Vf locus has revealed that it contains several receptor‐like Vf candidate genes. In order to determine which of these genes is most closely linked to Vf resistance, primers were designed based on conserved regions in the Vf candidate genes adjacent to a variable portion of the leucine‐rich repeat (LRR) domain, to yield PCR product length polymorphisms. PCR products were obtained from 31 cultivars of M. × domestica, of which 19 are known to contain Vf resistance, and from 10 selections of M. floribunda. PCR products corresponding in size to Vfa1 and Vfa2 were found in all the plants tested. However, a PCR product with 100% predicted amino acid identity to Vfa4 was found only in M. ×domestica cultivars known to have Vf scab resistance. This PCR product was also found in most, but not all, selections of M. floribunda tested, including the original source of Vf resistance, M. floribunda 821. The PCR product matching Vfa4 appears to be the most closely linked to Vf resistance and should be a valuable tool for monitoring Vf inheritance in apple.
Relationship of genetic structure of Pseudomonas savastanoi pv. savastanoi populations from Italian olive trees and patterns of host genetic diversity
Authors: Scortichini M. , Rossi M. P. , Salerno M.
Published: August 2004

A total of 360 Pseudomonas savastanoi pv. savastanoi isolates obtained from 11 Italian olive (Olea europaea) cultivars grown in different provinces were assessed with repetitive PCR using short interspersed elements of the bacterial genome as primers (ERIC, BOX and REP primer sets). The population structure of the isolates was determined by using three different hierarchical clustering algorithms: UPGMA, single‐link and complete‐link methods. REP primers were the most discriminatory. The various fingerprints obtained from the same cultivar and locality persisted over 2 years of knot sampling. Repetitive PCR and UPGMA analysis, using the three data sets combined, revealed 20 patterns with an overall similarity of 81%, with no grouping of the isolates. The resulting dendrogram shows a bush‐like topology. Similar results were obtained with the other two clustering methods. In contrast, data obtained from the literature showed that the genetic structure of olive is characterized by bifurcated dendrograms and clear grouping of cultivars. Therefore it appears that the host plant and its pathogen did not cospeciate. The strict adaptation of the bacterium to olive would represent a case of association by colonization.
Differential invasion of Candida albicans isolates in an in vitro model of oral candidosis
Authors: Bartie K. L. , Williams D. W. , Wilson M. J. , Potts A. J. C. , Lewis M. A. O.
Published: August 2004

The study assessed the ability of Candida albicans isolates to invade an in vitro oral tissue model. The extent and pattern of isolate invasion was then correlated with the infection origin of the isolate to identify characteristics that may be restricted to specific forms of oral infection, particularly chronic hyperplastic candidosis (CHC). Reconstituted human oral epithelium was infected with C. albicans isolated from normal oral mucosa (n = 4), CHC (n = 7), non‐CHC oral candidoses (n = 4) and squamous cell carcinoma (SCC; n = 4). After infection for 24 h, histological analysis revealed yeast adhesion, hyphal extension, and invasion of the epithelium. Differential patterns of invasion were evident and, whilst consistent for a given isolate, did not relate to the infection origin of the isolate. Two principal patterns of invasion were evident and described as either a ‘localised’ or a ‘uniform’ distribution of invading hyphae. Several isolates also exhibited superficial infection with limited hyphal invasion. In conclusion, the use of the in vitro tissue model allowed the assessment of the invasive capabilities of isolates of C. albicans. However, the apparent differences in invasive characteristics did not appear to be related to the clinical origin of isolates.
In vitro antimicrobial effect of bacteriophages on human dentin infected with Enterococcus faecalis ATCC 29212
Authors: Paisano A. F. , Spira B. , Cai S. , Bombana A. C.
Published: August 2004

This study assessed the effect of bacteriophages on the viability of Enterococcus faecalis. Human dental roots were inoculated with a suspension of E. faecalis at three different multiplicities of infection − 0.1, 1.0 and 10.0. The phage lysate was able to significantly inhibit bacteria growth when incubated at the multiplicities of infection of 1.0, 10.0 and 0.1. The dental roots were also inoculated with bacteria for 6 days to allow bacterial penetration into the teeth tubules. Addition of the phage lysate to the roots following the 6‐day incubation period led to a substantial reduction in bacteria viability. Phage therapy may be an important alternative for the treatment of root canal infections refractory to conventional endodontic therapy.
Pale, poor, and ‘pretubercular’ children: a history of pediatric antituberculosis efforts in France, Germany, and the United States, 1899–1929
Authors: Connolly Cynthia
Published: August 2004

An international consensus emerged in the years between 1900 and 1910 regarding the need to refocus antituberculosis efforts away from treating tuberculosis in adults and toward preventing active disease in children. This paper uses social history as a framework to explore pediatric health experiments in France (foster placement of city children with rural farm families), Germany (open‐air schools), and the United States (preventorium) for children considered ‘pretubercular’. The scientific, social, and political variables that reshaped prevailing ideas and practice with regard to TB prevention during those years are described. The creation of the first preventorium in the United States is explained and the way in which French and German pediatric prevention strategies were adapted to address a specific population considered at high risk in the United States, indigent immigrants, is detailed. For each of these three nations, nurses were central actors. Their efforts provide a unique vantage point to study the cultural dimensions of risk and prevention embedded in nursing care and the interplay between science, culture, nurses, and the state.
Motivations and barriers of foreign R&D activities in China
Authors: Gassmann Oliver , Han Zheng
Published: August 2004

The continued growth of the Chinese economy accompanied with the expansion of international investment in China has led to an increase in foreign research and development (R&D) activities in the country. Aside from the rising importance of R&D internationalization, research on foreign R&D in China has been neglected in the past due to its emerging status. In this article we examine drivers and barriers for conducting R&D in China. The focus of our research is on transnational companies typically characterized by decentralized R&D activities. Our research is mainly based on qualitative interviews with senior R&D managers. The success of foreign R&D activities in China strongly depends on the realistic estimation of its advantages and the proper identification and handling of barriers.
Day‐to‐day glucose variability during pregnancy in women with Type 1 diabetes mellitus: glucose profiles measured with the Continuous Glucose Monitoring System
Authors: Kerssen Anneloes , de Valk Harold W. , Visser Gerard H.A.
Published: August 2004

Objective  To observe day‐to‐day variability in glucose levels in pregnant women with Type 1 diabetes using the Continuous Glucose Monitoring System (CGMS) and to assess the usefulness of continuous glucose measurements for adjustment of insulin treatment.

Design  A prospective observational study.

Setting  The obstetrical outpatient clinic of the University Medical Centre Utrecht.

Population  Pregnant women with Type 1 diabetes mellitus.

Methods  Thirty‐one pregnant women with Type 1 diabetes used the CGMS for two consecutive days. Patients were classified in two groups (high vs low day‐to‐day variability) based on visual inspection of the glucose excursions. The relationship between day‐to‐day variability and the variables HbA1c, maternal age and body mass index (BMI), duration of diabetes, number of self‐monitored blood glucose levels, number of insulin injections, gestational age, nutrition, physical activity, White classification, living with children and method of insulin administration was determined. The two days of the first 20 CGMS measurements were separated and four physicians were asked to give recommendations on treatment adjustment for each separate day.

Main outcome measures  Mean absolute difference (MAD) was calculated for each patient as measure of day‐to‐day variability.

Results  Seventeen patients (55%) were classified as having low (MAD 0.92–2.33 mmol/L) and 14 (45%) as having high day‐to‐day variability (MAD 2.41–6.12 mmol/L). Of the variables measured, only the relation between MAD and HbA1c was significant (r= 0.58, P= 0.001). The difference in recommendation on treatment adjustment between the days of the CGMS measurement ranged from 29% to 48%. This percentage was significantly higher in the high day‐to‐day variability group (48 vs 33%, P= 0.01).

Conclusion  Day‐to‐day glucose variability is high and the treatment of pregnant women with Type 1 diabetes is a problem. Fine‐tuning of insulin regimens based on two‐day measurements with the CGMS is not advisable.
Low concentrations of maternal thyroxin during early gestation: a risk factor of breech presentation?
Authors: Pop Victor J. , Brouwers Evelien P. , Wijnen Hennie , Oei Guid , Essed Gerard G. , Vader Huib L.
Published: August 2004

Objective  To evaluate the relation between breech position at term (>37 weeks of gestation) and low maternal fT4 levels during gestation in women not suffering from overt thyroid dysfunction.

Design  A prospective cohort study of pregnant women.

Setting  Community‐based study.

Population/Sample  At random selected pregnant women of the general population.

Methods  At antenatal booking, based on thyroid function assessed at 12 weeks of gestation in a large cohort of pregnant women, two groups of participants were defined: women with low fT4 levels—below the 10th centile (n= 135) and women with fT4—between the 50th and 90th centiles at 12 weeks of gestation (n= 135). Women with clinical thyroid dysfunction (fT4 and TSH outside reference range) at 12 weeks of gestation were excluded. Maternal thyroid function (fT4 and TSH) was subsequently assessed at 24 and 32 weeks of gestation. Analysis refers to 204 women who met the inclusion and exclusion criteria and in whom all thyroid parameters were assessed.

Main outcome measures  Fetal presentation (cephalic–breech) at delivery in women with term gestation (>37 weeks of gestation) in relation to maternal thyroid function at 12, 24 and 34 weeks of gestation.

Results  Breech presentation at term delivery was independently related to fT4 levels <10th centile at 12 weeks of gestation (OR = 4.7, 95% CI 1.1–19 [but not to an fT4 level below the 10th centile at 24 and 32 weeks of gestation]) as well as primiparity (OR = 4.7, 95% CI 1.3–15).

Conclusions  Women with hypothyroxinaemia (fT4 level at the lowest 10th centile) during early gestation but without overt thyroid function are at risk for fetal breech presentation at term (>37 weeks of gestation).
Improving the quality of cervical screening
Authors: George Samuel , Abrahams Yusuf , Karim Shakir Z. , Kothari Anjali
Published: August 2004

Objective  To compare the adequacy of cervical cytology sampling by a newly designed cervical cell sampler (the implement) with a commonly used, extended tip cervical scraper, namely the Jordan's spatula, by assessing the quality of cervical smears obtained.

Design  Prospective randomised controlled trial, with the approval of the local Ethics Committee after informing the Medical Devices Agency in the UK.

Setting  Colposcopy Clinic in a District General NHS Trust Hospital in London.

Population  Women attending the Colposcopy Clinic and having a good command of the English language (to avoid any misinterpretation of the information and enabling them to give informed consent) were invited to take part. Two hundred and twenty patients were recruited.

Methods  The women were randomised into two groups, each of them having two smears at the same time, half of them having their first smear with the Jordan's spatula and the other half having the first smear with the new implement.

Main outcome measure  Good quality smears, assessed by evidence of effective sampling of the transformation zone, including immature metaplastic cells and also endocervical cells.

Results  Fifty‐four percent of smears taken by the new implement showed good quality smears, compared with 37% taken by Jordan's spatula, a statistically significant result with P value <0.001.

Conclusion  A larger number of good quality smears, judged by evidence of sampling of transformation zone and presence of endocervical cells, were obtained with the new implement. The difference was statistically significant. This would enhance the ability to detect dyskaryosis and increase adequate smear rates, reducing unnecessary recall of patients for repeat smears.
A randomised trial comparing open Burch colposuspension using sutures with laparoscopic colposuspension using mesh and staples in women with stress urinary incontinence
Authors: Ankardal Maud , Ekerydh Anne , Crafoord Kristina , Milsom Ian , Stjerndahl Jan‐Henrik , Engh Marie Ellström
Published: August 2004

Objective  To compare open Burch colposuspension using sutures with laparoscopic colposuspension using mesh and staples in women with stress urinary incontinence.

Design  Multicentre, prospective randomised trial.

Setting  Departments of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Göteborg, Borås County Hospital and Örebro University Hospital, Sweden.

Population  Women with genuine stress urinary incontinence or mixed incontinence with a predominantly stress component were included, and were randomised to either open colposuspension (n= 120) or laparoscopic colposuspension (n= 120).

Methods  Women were randomised to open colposuspension with sutures or laparoscopic colposuspension with polypropylene mesh and staples. Anaesthesia/operation time, blood loss, complications and other related surgical parameters were compared.

Main outcome measures  Objective and subjective cure rates from 48‐hour frequency–volume chart, a 48‐hour pad test and a subjective assessment of the woman's incontinence and quality of life performed one year after surgery.

Results  Objective and subjective cure rates were higher after open compared with laparoscopic colposuspension (P < 0.001). Quality of life was improved following surgery in both groups (P < 0.0001) and the improvement was significantly greater in the open colposuspension group (P < 0.05) with regard to physical activity. Performing an open colposuspension was less time consuming (P < 0.0001), resulted in more blood loss (P < 0.0001), longer catheterisation time (P < 0.01), greater risk of urinary retention (P < 0.01) and a longer hospital stay (P < 0.0001) compared with performing a laparoscopic colposuspension. The rate of serious complications was low in both groups.

Conclusion  Open colposuspension had a higher objective and subjective cure rate one year after surgery but with a greater blood loss, greater risk of urinary retention and a longer hospital stay than laparoscopic colposuspension.
T594M mutation of the epithelial sodium channel β‐subunit gene in pre‐eclampsia and eclampsia in Black South African women
Authors: Pegoraro R.J. , Roberts C.B. , Rom L. , Moodley J.
Published: August 2004

The possible role of the β‐subunit of the epithelial sodium channel T594M polymorphism in hypertensive disorders of pregnancy has not been examined. This study compared Black South African women with pre‐eclampsia (n= 204), early onset pre‐eclampsia (n= 67), eclampsia (n= 120) and gestational hypertension (n= 78) with 338 women from the same ethnic group who had full‐term normotensive pregnancies, for the presence of the T594M polymorphism. The variant allele was detected in 1.7% to 3.8% of the various patient groups and in 3.6% of the control group reflecting no significant difference. These results suggest that the T594M polymorphism in the sodium channel β‐subunit is not associated with the pathogenesis of pre‐eclampsia or gestational hypertension.
A prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy
Authors: Tang Oi Shan , Lau Winnie Nga Ting , Chan Carina Chi Wai , Ho Pak Chung
Published: August 2004

Objective  To compare the efficacy, side effects and acceptability of sublingual and vaginal misoprostol for second trimester medical abortion.

Design  Prospective randomised controlled trial.

Setting  Tertiary referral unit and a teaching hospital.

Population  Two hundred and twenty‐four women at 12 to 20 weeks of gestation.

Methods  The women were randomised to receive either sublingual or vaginal misoprostol 400 μg every 3 hours for a maximum of five doses. The course of misoprostol was repeated if the woman did not abort within 24 hours.

Main outcome measures  The success rate at 48 hours, induction‐to‐abortion interval and the side effects.

Results  There was no significant difference in the success rate at 48 hours (sublingual: 91%; vaginal: 95%). However, the success rate at 24 hours was significantly higher in the vaginal group (85%) compared with the sublingual group (64%). There was no difference in the median induction‐to‐abortion interval (sublingual: 13.8 hours; vaginal: 12.0 hours). Significantly more women in the sublingual group preferred the route to which they were assigned when compared with the vaginal group. The incidence of fever was also less in the sublingual group.

Conclusion  The use of vaginal misoprostol for second trimester medical abortion resulted in a higher success rate than sublingual misoprostol at 24 hours but the abortion rate was similar at 48 hours. Vaginal misoprostol should be the regimen of choice but sublingual misoprostol is also an effective alternative.
The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre‐eclampsia
Authors: Merchant Shaila J. , Davidge Sandra T.
Published: August 2004

Objectives  (1) To investigate the effects of plasma from non‐pregnant, normal pregnant and pre‐eclamptic women on myogenic tone and endothelium‐dependent relaxation; (2) To investigate the role of matrix metalloproteinases (MMPs) in these parameters of vascular function.

Design  Analysis of the effects of plasma from non‐pregnant, normal pregnant and pre‐eclamptic women on myogenic tone and endothelium‐dependent relaxation, and the effects of MMP inhibition on these parameters.

Setting  University of Alberta, Edmonton, Alberta, Canada.

Samples  Pooled plasma from non‐pregnant (n= 9), normal pregnant (n= 6) and pre‐eclamptic women (n= 12).

Methods  Mesenteric arteries from virgin female C57BL/6J mice were exposed to pooled plasma from non‐pregnant, normal pregnant and pre‐eclamptic women in the absence and presence of GM6001 (5 μM; MMP inhibitor), and arterial function was assessed.

Main outcome measures  Myogenic tone and endothelium‐dependent relaxation.

Results  Plasma of women with pre‐eclampsia, and interestingly, plasma of non‐pregnant women, significantly enhanced myogenic tone at pressures ≥70 mmHg (P < 0.001) and blunted the maximum relaxation to methacholine (P < 0.001; P < 0.005) in isolated arteries. GM6001 altered response only in vessels exposed to the plasma of women with pre‐eclampsia; however, contrary to our hypothesis, this further enhanced myogenic tone and further abrogated relaxation.

Conclusions  The strikingly similar vascular function profiles of vessels incubated in the plasma of non‐pregnant and pre‐eclamptic women suggest that pre‐eclampsia may be due, in part, to the lack of a necessary adaptation to pregnancy. Despite these similarities, however, there are differential effects of MMP inhibition, suggesting that MMPs play a greater role in the vasculature of women with pre‐eclampsia compared with non‐pregnant and normal pregnant women.
Early‐onset neonatal group B streptococcal infection in London: 1990–1999
Authors:   on behalf of the Health Protection Agency Group B Streptococcus Working Group, Mifsud Albert J. , Efstratiou Androulla , Charlett André , McCartney A. Christine
Published: August 2004

Objective  To identify the incidence of early‐onset group B streptococcal infection and to describe the antecedent maternal risk factors, in order to provide data to inform the design of interventional strategies that could be introduced in the UK to reduce the burden of this infection.

Design  A retrospective study with review of case notes of mothers and babies.

Setting  Seven maternity units in London during 1990–1999.

Population  All cases of proven early‐onset neonatal group B streptococcal infection.

Methods  Identification of presence of risk factors that could be used to select women for the offer of intrapartum antibiotic prophylaxis.

Main outcome measures Incidence and case‐fatality rate of invasive early‐onset group B infection.

Results  One hundred and forty cases were identified among a birth cohort of 198,388 live births, an incidence of 0.71 per 1000 live births. Twenty‐two babies died, a case‐fatality rate of 15.6% or 1.1 per 100,000 live births. Women of black ethnic origin, and those who had had a previously affected infant, multiple pregnancy, preterm delivery, prolonged rupture of membranes or intrapartum fever all had a significantly increased risk of delivering an infected infant.

Conclusions  These data suggest that the incidence of early‐onset group B streptococcal infection in these London centres is sufficiently high to warrant administration of intrapartum antibiotics to at‐risk women.