bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo and in vitro immunomodulation of Der p 1 allergen‐specific response by Lactobacillus plantarum bacteria
Authors: Hisbergues M. , Magi M. , Rigaux P. , Steuve J. , Garcia L. , Goudercourt D. , Pot B. , Pestel J. , Jacquet A.
Published: August 2007

Background
Lactic acid bacteria (LAB) were reported to reduce some allergic manifestations in mice and humans but their impact on the aeroallergen‐dependent immune mechanisms is still debated.

Objective
The potential capacities of Lactobacillus plantarum NCIMB8826 to reduce the allergic response induced by Der p 1, the major house dust mite allergen of Dermatophagoides pteronyssinus, were evaluated in vivo and in vitro.

Methods
First, the effect of the intranasal co‐administration of LAB and purified Der p 1 allergen before a sensitization protocol was evaluated. The allergen‐specific antibody and cellular responses as well as airway inflammation were measured. Second, the impact of LAB on the cytokine profile of spleens cells from Der p 1‐sensitized mice was assessed. Third, upon stimulation with LAB, the levels of cytokine produced by dendritic cells derived from the bone marrow (BMDCs) of wild‐type, Toll‐like receptor 2 (TLR2)‐, TLR4‐ and MyD88‐KO mice were compared.

Results
The co‐application of L. plantarum and Der p 1 induced a T‐helper type 1 (Th1)‐biased allergen‐specific IgG response, the absence of specific IgE response and favoured the production of INF‐γ upon allergen re‐stimulation. Moreover, the previous LAB administration reduced the development of bronchoalveolar lavage eosinophilia usually induced by aerosol exposure. Additionally, the studied LAB strain was shown to modify in vitro the cytokine level produced by Der p 1‐sensitized spleen cells mainly towards a Th1 profile. Finally, L. plantarum stimulated high IL‐12 and moderate IL‐10 production in mouse BMDCs notably through the TLR2‐, MyD88‐dependent and TLR4‐independent pathway.

Conclusion
In vivo co‐administration of probiotic LAB with Der p 1 might prevent the development of the mite allergic response. The probiotic L. plantarum was shown to display in vitro therapeutic potentials for the treatment of allergy and to trigger the immune system by a TLR2‐ and MyD88‐dependent signalling pathway.
Early predictors for developing allergic disease and asthma: examining separate steps in the ‘allergic march’
Authors: Almqvist C. , Li Q. , Britton W. J. , Kemp A. S. , Xuan W. , Tovey E. R. , Marks G. B. ,   for the CAPS team
Published: August 2007

Background
Sensitization and symptoms of allergic disease are strongly correlated, but little is known about the early clinical precursors of the development of allergen sensitization in childhood. The aim of this study was to identify these predictors, and to examine separately the effect of early sensitization on subsequent wheeze, asthma, rhinitis and eczema.

Methods
In the Childhood Asthma Prevention Study, children with a family history of asthma were assessed for allergen sensitization, total serum IgE, wheeze, asthma, eczema and rhinitis at ages 18 months and 5 years. To examine predictors, at 18 months, for subsequent sensitization, children who were non‐sensitized at 18 months and had data on sensitization at 5 years were investigated, n=375. To examine the predictors, at age 18 months, of subsequent onset of symptoms, children who did not have wheeze, asthma, eczema or rhinitis at 18 months were followed‐up at 5 years, n=177.

Results
Among children who were non‐sensitized at age 18 months, the presence of eczema [adjusted relative risk (aRR), 1.67, 95% confidence interval (CI) 1.20–2.33], but not wheeze, asthma or rhinitis, was an independent predictor of the onset of sensitization by age 5 years. Among children who were asymptomatic at age 18 months, sensitization to any allergen at 18 months was an independent predictor for the presence of wheeze (aRR 2.41, 95% CI 1.28–4.55), asthma (aRR 4.66, 95% CI 1.88–11.54) and rhinitis (aRR 1.77, 95% CI 1.08–2.90), but not for the development of eczema (aRR 0.78, 95% CI 0.23–2.64) at 5 years.

Conclusion
In non‐sensitized children, eczema, but not wheeze, asthma or rhinitis is a predictor for subsequent development of sensitization. This suggests that early childhood eczema, rather than wheeze and rhinitis, may promote subsequent allergen sensitization and raises the possibility that early management of eczema may reduce the prevalence of sensitization in children.
Regulation of German cockroach extract‐induced IL‐8 expression in human airway epithelial cells
Authors: Lee K. E. , Kim J. W. , Jeong K. Y. , Kim K. E. , Yong T. S. , Sohn M. H.
Published: August 2007

Background
Cockroaches have been known as a cause of respiratory allergies such as asthma. IL‐8 plays an integral role in the coordination and persistence of the inflammatory process in the chronic inflammation of the airways in asthma.

Objective
We investigated the mechanism by which German cockroach extract (GCE) triggers IL‐8 release from human airway epithelial cells.

Methods
Chemical inhibitors were pretreated before addition of GCE for promoter activity and protein synthesis of IL‐8. The Transcriptional activity of IL‐8 promoter was analysed by mutational, deletional anaylsis and electrophoretic mobility shift assay (EMSA).

Results
Stimulation of H292 cells with GCE resulted in a time‐ and concentration‐dependent induction of IL‐8 transcription and protein synthesis. IL‐8 promoter deletion analysis indicated that position −132 to +41 was essential for GCE‐induced IL‐8 transcription, and mutants with substitutions in activator protein (AP)‐1, nuclear factor (NF)‐IL6 and NF‐κB‐binding sites revealed a requirement for NF‐κB and NF‐IL6, but not AP‐1, in GCE‐induced activation of the IL‐8 promoter. The DNA‐binding activities of NF‐κB and NF‐IL6 were induced by GCE, as determined by EMSA. The chemical inhibition of extracellular signal‐regulated kinase (ERK) attenuated GCE‐induced transcriptional activity and protein synthesis. In addition, through aprotinin treatment and PAR2 small interfering RNA transfection, it was proven that protease of GCE is consistent with the regulation of GCE‐induced IL‐8.

Conclusion
We conclude that GCE with protease activity‐induced IL‐8 expression is regulated by transcriptional activation of NF‐κB and NF‐IL6 coordinating with the ERK pathway in human airway epithelial cells.
Association between candidate genes and lung function growth in Chinese asthmatic children
Authors: Leung T. F. , Chan I. H. S. , Wong G. W. K. , Li C. Y. , Tang N. L. S. , Yung E. , Lam C. W. K.
Published: August 2007

Background
Asthma is caused by a complex interaction between multiple candidate genes and environmental factors. The Childhood Asthma Management Program reported lung function decline in a significant proportion of Caucasian asthmatic children, but such a relation has not been studied in other populations. Our group recently reported that interleukin‐13 (IL13), interleukin‐4 receptor‐α and thymus and the activation‐regulated chemokine interacted to influence asthma and raised plasma total IgE. However, there has not been any study that has addressed the genetic influences for longitudinal lung function growth.

Objective
We studied the longitudinal changes in spirometric variables in Chinese asthmatic children, and investigated the influence and interactions between eight different loci in six candidate genes as well as environmental factors affecting lung function growth in these children.

Methods
Spirometry was performed at baseline and study completion. Genotyping was performed by restriction fragment length polymorphism. Multi‐factor dimensionality reduction (MDR) was used to detect any gene–gene or gene–environment interaction.

Results
We prospectively followed 131 Chinese children, aged 9.9 (3.0) years, for 4.5 (0.8) years. Their mean (standard deviation) baseline forced expiratory volume in 1 s (FEV1) was 98.6 (20.6)% of predicted, and FEV1 to forced vital capacity (FVC) ratio was 77.8 (11.3)%. FEV1 and FVC increased by 210 (115) and 248 (148) mL/year during this study, and these changes were significantly larger among males (P<0.0001). Univariate analysis revealed a significant association between annual FEV1 change and C1570T of signal transducer and activator of transcription 6 gene (STAT6; P=0.009). Linear regression confirmed this finding (P=0.041). Using MDR, we detected a significant 3‐locus interaction between IL13 R130Q, ADRB2 R16G and STAT6 C1570T for determining change in FVC (P=0.045).

Conclusion
Our data suggest that STAT6 may influence lung function growth in asthmatic children. We also found significant interactions among several atopy‐related genetic polymorphisms for influencing FVC change.
Serum fasting cortisol in relation to bone, and the role of genetic variations in the glucocorticoid receptor
Authors: Van Schoor N. M. , Dennison E. , Lips P. , Uitterlinden A. G. , Cooper C.
Published: August 2007

Objective  To examine the relationship between endogenous cortisol and bone, and the role of genetic variations in the glucocorticoid receptor (GR).

Design and patients  The Longitudinal Ageing Study Amsterdam (LASA), a population‐based cohort study in older men and women.

Measurements  Serum fasting cortisol was assessed by competitive immunoassay (n = 1214); bone mineral density (BMD) by dual X‐ray absorptiometry (DXA) (n = 502); broadband ultrasound attenuation (BUA) by ultrasound (n = 1209); fractures by self‐report (n = 1211); and GR gene polymorphisms (ER22/23EK, N363S, 9beta, BclI) were genotyped by Taqman (n = 858).

Results  Higher serum fasting cortisol was significantly associated with lower BMD at all sites and BUA at the heel in women, although most relationships were attenuated by age and body mass index (BMI). The effect on femoral neck BMD remained statistically significant in the fully adjusted model (r = –0·135, P = 0·04). No significant associations in men were found. Female 9beta G‐allele carriers had 50·2 nmol/l lower cortisol and 1·2 lower free cortisol levels than AA homozygotes [P = 0·01 for (free) cortisol]. Furthermore, female BclI GG homozygotes had 54·8 nmol/l higher cortisol levels than C‐carriers (P = 0·03). In the total population, BclI GG homozygotes had 0·05 g/cm2 lower trochanteric region BMD (P = 0·03). For the other GR gene polymorphisms, no significant associations were found.

Conclusions  Higher cortisol levels are associated with lower femoral neck BMD in elderly women. The G allele of the 9beta polymorphism was associated with lower serum cortisol levels in women. Female BclI GG homozygotes had higher serum cortisol levels, and BclI GG homozygotes had lower trochanteric region BMD in the total population.
Factors associated with elevated serum concentrations of anti‐TPO antibodies in subjects with and without diffuse goitre. Results from the Ukrainian–American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Accident
Authors: McConnell Robert J. , Brenner Alina V. , Oliynyk Valery A. , Robbins Jacob , Terekhova Galyna M. , Fink Daniel J. , Epshtein Ovsiy V. , Hatch Maureen , Shpak Victor M. , Brill A. Bertrand , Shelkovoy Yevgeniy A. , Zablotska Lydia B. , Masnyk Ihor J. , Howe Geoffrey R. , Tronko Mykola D.
Published: August 2007

Objectives  To examine factors associated with the prevalence of elevated anti‐thyroid peroxidase antibodies (ATPO) among iodine‐deficient adolescents and young adults and test whether associations vary according to the presence of diffuse goitre.

Design  Subjects were members of the Ukrainian–American Cohort Study exposed to the Chornobyl accident whose 131I thyroid dose estimates were below 0·2 Gy.

Measurements  The odds ratios (ORs) for ATPO above 60 U/ml were estimated using logistic regression models for a number of factors in the total population (N = 5133), and separately for thyroid disease‐free subjects (N = 3875), those with diffuse goitre (N = 921), and diffuse goitre without autoimmune thyroiditis (AIT; N = 883).

Results  Elevated ATPO was found in 9·9% of the total population and ORs were significantly higher in females, older individuals, those examined in earlier calendar years, residents of Kyiv and Chernihiv oblasts, subjects with a family history of thyroid disease, higher thyroid ultrasound volume, suppressed or elevated TSH, blood collection in March to May, very low thyroglobulin (Tg), and shorter serum storage time. When thyroid disease‐free subjects and those with diffuse goitre were compared, there were few differences in antibody prevalence, and after excluding individuals with AIT, the only difference was an increased prevalence of elevated ATPO at low urinary iodine in those with goitre alone.

Conclusions  Although a number of factors are associated with the prevalence of elevated ATPO in our study group, with the exception of urinary iodine these factors are independent of goitre, and differences between thyroid disease‐free subjects and those with diffuse goitre are largely due to AIT.
Changes and relationships of IGFS and IGFBPS and cytokines in coeliac disease at diagnosis and on gluten‐free diet
Authors: Street Maria E. , Volta Cecilia , Ziveri Maria A. , Zanacca Claudio , Banchini Giacomo , Viani Isabella , Rossi Maurizio , Virdis Raffaele , Bernasconi Sergio
Published: August 2007

Objective  To evaluate changes and relationships of IGFs and IGFBPs, serum interleukin 6 (IL‐6) and tumour necrosis factor (TNF)‐α, and auxological parameters at diagnosis of coeliac disease (CD) and at 6 months and 12 months after starting a gluten‐free diet (GFD), compared with a control population.

Patients  Twenty patients were enrolled at diagnosis (9 male, 11 female; age 9·6 ± 0·8 years). A healthy population of 18 subjects (5 male, 13 female; age 11·3 ± 0·6 years) comparable for age, sex and pubertal status served as controls at baseline.

Measurements  Blood samples were taken at diagnosis, and at 6 months and 12 months after starting the GFD. Serum IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2, IGFBP‐3, IL‐6 and TNF‐α were measured using commercial kits. Height (Ht) standard deviation score (SDS), body mass index (BMI) SDS and Ht velocity SDS were evaluated at diagnosis and at 6 months and 12 months after starting GFD.

Results  In CD patients, both Ht SDS and BMI SDS increased during the first year of treatment, and Ht velocity SDS increased during the second 6 months of follow‐up (P < 0·05). At diagnosis, IGF‐I, IGF‐II and IGFBP‐3 were lower compared with controls, IGFBP‐1 was similar, IGFBP‐2, IL‐6 and TNF‐α were higher (P < 0·05). When on GFD, all peptides normalized and IGFBP‐1 decreased. The IGF‐I/IGFBP‐2 and IGF‐I/IGFBP‐3 molar ratios were significantly reduced at diagnosis compared with those of controls, but were increased for both groups when on GFD. Although there was no apparent abnormality at diagnosis, the IGF‐II/IGFBP‐2 molar ratio increased significantly on GFD. Ht velocity SDS was positively correlated with IGFBP‐3 (P < 0·05) and with the IGF‐I/IGFBP‐2 molar ratio (P < 0·05). Serum IL‐6 was negatively correlated with IGF‐I and positively with IGFBP‐1 (P < 0·05).

Conclusions  The data obtained from this study confirm changes in the IGF and cytokine systems at diagnosis of CD which tend to normalize on the gluten‐free diet. The two systems show relationships with each other and with linear growth.
Prospective evaluation of a protocol for reduced glucocorticoid replacement in transsphenoidal pituitary adenomectomy: prophylactic glucocorticoid replacement is seldom necessary
Authors: Wentworth John M. , Gao Nicole , Sumithran Kalpana P. , Maartens Niki F. , Kaye Andrew H. , Colman Peter G. , Ebeling Peter R.
Published: August 2007

Background  Most pituitary surgery centres prescribe perioperative glucocorticoids to subjects undergoing transsphenoidal pituitary adenomectomy (TSA), despite reports suggesting this may be unnecessary. Evidence‐based guidelines for glucocorticoid use in TSA have recently been published but there are no prospective studies of their utility.

Objective  To implement and assess a protocol for reduced glucocorticoid replacement for subjects undergoing TSA.

Design  Prospective and retrospective cohort study in an Australian pituitary surgery centre.

Patients and measurements  Clinical and biochemical data for 56 TSAs performed for non‐ACTH‐secreting tumours between March 2004 and April 2006 were prospectively collected and compared with data for 47 TSAs performed between October 2001 and November 2003, before implementation of the protocol. In the prospective cohort, a postoperative days 1–3 morning serum cortisol threshold of 250 nmol/l (91 µg/dl) was used to guide long‐term glucocorticoid requirement.

Results  Implementation of the protocol was associated with significant reductions in dose and duration of glucocorticoid treatment post TSA in 44 ‘low‐risk’ cases (no preoperative glucocorticoid use or evidence of pituitary apoplexy). In two low‐risk cases, long‐term glucocorticoid replacement was required despite postoperative cortisol greater than 250 nmol/l. Following the remaining 42 low‐risk operations, glucocorticoid was not prescribed on hospital discharge on the basis of morning serum cortisol > 250 nmol/l and no clinical evidence of hypocortisolism. None of these 42 cases required glucocorticoid treatment for hypocortisolism following surgery. Short synacthen tests were performed in 35 of these subjects a minimum of 6 months after surgery and were normal. Use of the protocol was not associated with differences in postoperative complications.

Conclusions  Reduced glucocorticoid replacement in TSA is safe and reduces patient exposure to glucocorticoids and their potential adverse events. The occurrence of hypocortisolism in two low‐risk subjects with serum cortisol > 250 nmol/l highlights the importance of daily clinical assessment when using this protocol.
Age trends in pre‐cancerous and cancerous lesions of the uterine cervix in a cytology screening programme: what should be the target age group for a major thrust of screening in resource‐limited settings?
Authors: Gupta S. , Sodhani P. , Halder K. , Chachra K. L. , Singh V. , Sehgal A.
Published: August 2007

Objective:  To identify the target age group where screening efforts may be concentrated in order to reduce the incidence of cervical cancer in resource‐limited countries.

Study design:  The results of cyto‐screening in a hospital‐based screening programme for early detection of cervical cancer were analysed retrospectively. The frequency of epithelial cell abnormalities (ECAs) was computed in different age groups.

Observations and results:  A total of 5.6% ECAs were detected on cyto‐screening. The peak age incidence for squamous intraepithelial lesions (SILs) was in the 30–39 age group while that for malignancies was age >60 years. The mean ages for LSIL, HSIL and cancer were 34.7, 37.7 and 51.8 years respectively. Around 43% LSILs and 48% HSILs presented in the fourth decade. If both fourth and fifth decade are covered by screening we could detect almost two‐thirds of SILs.

Conclusions:  A distinct latent period of more than a decade between the onset of SIL and development of frank cancer provides us with ample opportunity to prevent cervical cancer through screening. Our data validate the WHO recommendation of once in a lifetime screening of women in their fourth decade, for low‐resource settings. If resources permit, screening can be extended to include women in the fifth decade. This approach would enable us to pick up maximum SILs within the available resources and prevent their progression to cancer.
Exposure to alcohol or tobacco affects the pattern of maturation in oral mucosal cells: a cytohistological study
Authors: Burzlaff J. B. , Bohrer P. L. , Paiva R. L. , Visioli F. , Sant’Ana Filho M. , Da Silva V. D. , Rados P. V.
Published: August 2007

Objective: To assess the maturation pattern of oral mucosal cells of patients exposed to tobacco and alcohol.

Methods:  (i) Group without lesions. Smears obtained from the lower lip, border of the tongue and floor of the mouth of 31 control individuals (group I), 49 tobacco users (group II) and 27 tobacco/alcohol users (group III) were stained using the Papanicolaou method. The first 100 cells counted on each smear determined the maturation pattern and the keratinization index (KI). Analysis of variance (anova) and the Tukey multiple comparison test were used for statistical analysis, at a 5% significance level. (ii) Group with lesions. Cytopathological and histopathological studies were conducted for 15 patients: eight with leucoplakia without epithelial dysplasia, two with epithelial dysplasia and five with squamous cell carcinoma.

Results:  (i) Group without lesions. Statistical analysis revealed a smaller number of superficial cells with nuclei in all sites of the group of tobacco/alcohol users (group III) when compared to the control group (group I), and this difference was statistically significant (P < 0.005). (ii) Group with lesions. The severity of histopathological findings increased with the increase in the number of cells of the deeper epithelial layers, with a statistically significant difference in the number of intermediate (P = 0.013) and parabasal cells (P = 0.049), which increased with the severity of the epithelial maturation disorder: leucoplakias with dysplasia had a greater number of intermediate and parabasal cells than leucoplakias without dysplasia; and the number in squamous cell carcinomas was greater than in leucoplakias with dysplasia.

Conclusion:  The maturation pattern of cells in the three anatomic sites showed changes that may be associated with the synergistic effect of tobacco and alcohol. Also, the severity of histopathological findings was associated with the increase in the number of cells in the deeper epithelial layers.
Physical defence traits enhance seedling survival of neotropical tree species
Authors: ALVAREZ‐CLARE S. , KITAJIMA K.
Published: August 2007

Physical defence traits of stems and leaves should enhance biomechanical strength and survival of seedlings. For eight neotropical tree species that differ widely in life‐history strategies, we compared stem and leaf biomechanical traits of 1 and 7‐month‐old seedlings grown in the shaded forest understorey and in the laboratory.

Material traits (biomechanical traits per unit volume, mass or cross sectional area) were positively associated with seedling survival across species. Shade tolerant species that survive well in the forest understorey had stems and leaves with greater modulus of elasticity (stiffness), fracture toughness (resistance to tear), tissue density and fibre contents, compared to less shade tolerant species.

Seedling survival was most strongly correlated with stem tissue density at both 1 and 7 months (Spearman's correlation coefficient rs = 0·93 and 0·90), but was also strongly correlated with leaf density and stem toughness at 7 months (rs = 0·93 and 0·89, respectively).

Multiple material traits were strongly and positively correlated with each other in both stems and leaves. However, these traits varied independently of seed and seedling size among species, indicating the unique importance of physical defence as functional traits.

Structural traits of stems that integrate size with material traits, including % critical buckling height, flexural stiffness, work‐to‐bend and stem flexibility, showed no significant interspecific correlation with seedling survival.

Modulus of elasticity and fracture toughness of stems generally increased as seedlings aged from 1 to 7 months, especially in species with high tissue density. In contrast, fracture toughness of leaf mid‐vein and lamina showed inconsistent ontogenetic changes across species.

These results demonstrate that biomechanical traits including tissue density and fracture toughness should be considered as important functional correlates of seedling survival and overall life‐history strategies of tree species.
Adjustment of structure and function of Hawaiian Metrosideros polymorpha at high vs. low precipitation
Authors: CORNWELL W. K. , BHASKAR R. , SACK L. , CORDELL S. , LUNCH C. K.
Published: August 2007

Populations of Metrosideros polymorpha establish across a broad range of precipitation in Hawai‘i – from <400 to >10000 mm per year. To determine whether adjustment of hydraulic and photosynthetic traits could contribute to this success in both high and low rainfall, we sampled populations on the wet and the dry sides of Hawai‘i Island, replicated on two different‐aged lava flows at similar elevation and mean annual temperature.

We quantified 24 stem and leaf traits in an integrated study of hydraulics, gas exchange, leaf chemistry and anatomy.

Values for traits associated with capacity for water transport through the plant and gas exchange per leaf area were higher at dry sites, including photosynthetic capacity, nitrogen per leaf area and hydraulic conductivity on both sapwood area and leaf area basis. These adjustments, due to plastic and/or heritable differentiation, would partially compensate for generally lower water availability.

Specific leaf area shifted towards lower values at the dry sites. However, several other traits associated directly with drought tolerance were inflexible across sites, including stem vulnerability to embolism and leaf cuticular conductance, indicating that the ability to persist through dry periods is sustained across the species’ range.

The ability of M. polymorpha to establish across a wide range of habitats is associated with, on one hand, adjustments in traits that would enable sustained growth across a dramatic range of moisture supply while simultaneously maintaining as fixed other traits that would contribute to survival through extended drought.
Comparing prophylaxis with episodic treatment in haemophilia A: implications for clinical practice
Authors: MANCO‐JOHNSON M.
Published: August 2007

Summary.  Recurrent haemarthroses in patients with severe haemophilia A often result in irreversible joint damage. Treatment using routine infusions of factor VIII (FVIII) concentrate, a therapy known as prophylaxis, is currently recommended for the prevention of haemarthroses and arthropathy in persons with severe haemophilia A. However, until recently, the body of evidence supporting prophylaxis in comparison with FVIII infusions given only at the time of haemarthroses was mostly retrospective and anecdotal. Recently, two prospective randomized clinical trials have been conducted to compare prophylaxis with on‐demand FVIII treatment for the prevention of arthropathy and haemarthroses in young children with haemophilia A. A third prospective, non‐randomized trial evaluated a strategy of escalating the dose frequency of prophylaxis. Data from these studies will provide objective evidence for the prevention of haemarthroses and arthropathy in children with severe haemophilia A.
Enhancing lifestyle for individuals with haemophilia through physical activity and exercise: the role of physiotherapy
Authors: WITTMEIER K. , MULDER K.
Published: August 2007

Summary.  For individuals with haemophilia, the benefits of many forms of physical activity outweigh their risks. Although activities with significant trauma risk should be avoided, persons who have haemophilia can participate in, enjoy and even excel in a variety of physical activities and sports. Both the National Hemophilia Foundation and the World Foundation of Hemophilia have produced documents to guide individuals with haemophilia and their healthcare professionals, coaches and parents in developing physical activity programmes and participation in sports. Physical activity guidelines for promoting health benefits exist worldwide and can be incorporated into individualized exercise programmes to ensure that a person with haemophilia is not only choosing appropriate activities, but also improving overall health and preparing the body to manage haemophilia better. Physiotherapy treatment is paramount in helping individuals prevent, manage and optimally recover from bleeds. Furthermore, the physical therapist, along with the haemophilia care team, can assist in preparing an individual to begin or progress to a physical activity programme that enhances fitness level, body composition and overall well‐being. This article presents the unique role of the physiotherapist in facilitating safe participation in quality physical activity in the context of risks, benefits and activity recommendations. Participation in physical activity from an early age is ideal to facilitate the development of body awareness and capability and to foster the adoption of a physically active lifestyle; however, it is never too late to start. Consistent participation in quality physical activity beginning at any age is central to managing haemophilia and, equally important, to achieving overall health and well‐being.
Quality of life and sports activities in patients with haemophilia
Authors: VON MACKENSEN S.
Published: August 2007

Summary. Quality of life (QoL) is a multidimensional construct pertaining to an individual’s physical, emotional, mental, social and behavioural components of well‐being and functioning. QoL can be assessed using both generic and disease‐specific instruments. QoL assessment in haemophilia is a relatively new area of study; the first data were published in 1990 using generic QoL questionnaires. Only recently have haemophilia‐specific questionnaires been developed, first for children and then for adults. Because sports activities include not only physical and functional aspects, but also have an impact on an individual’s self‐esteem and social interactions, they should play an essential role in QoL assessment. Until the 1970s, persons with haemophilia were advised to avoid any kind of physical activity because of the risk of bleeds. Nowadays, however, the attitude towards sports for patients with haemophilia has changed, and the World Federation of Haemophilia has formulated recommendations concerning physical activities for patients with haemophilia. Although sports activities are recommended, their importance as an integral element in haemophilia management has not yet been widely recognized. Awareness of the importance of sports activities for this patient group has increased, and several sports projects are ongoing. For example, a twice‐annual sports camp for adult patients has been held in Germany for the past 2 years; and physical improvements, QoL and subjective training effects are being measured. Another study is investigating the prevalence of sports activities in Italian children with haemophilia and their attitudes towards sports and is also assessing QoL. In Israel, a study is planned in which haemophilic children will participate in a karate training programme, and a QoL evaluation will be added to the physical assessment. In conclusion, sports activities can improve not only physical well‐being, but also the emotional and social well‐being of persons with haemophilia and, therefore, should become part of the global approach to haemophilia management.
Improving estimation of liver fibrosis using combination and newer noninvasive biomarker scoring systems in hepatitis C‐infected haemophilia patients
Authors: MAOR Y. , CALÈS P. , BASHARI D. , KENET G. , LUBETSKY A. , LUBOSHITZ J. , SCHAPIRO J. M. , PÉNARANDA G. , BAR‐MEIR S. , MARTINOWITZ U. , HALFON P.
Published: August 2007

Summary.  Non‐invasive biomarkers have gained popularity for estimating fibrosis stage. In our hepatitis C‐infected haemophilia patients, Fibrotest (FT) correctly identified clinically advanced or minimal liver disease. More accurate tests, like the FibroMeters, have recently been validated. The aim of the study was to improve the estimation of liver fibrosis in hepatitis C‐infected haemophiliacs using a combination of biomarkers and FibroMeters. One hundred and thirty‐two hepatitis C‐infected haemophilia patients (124 male, mean age: 39 ± 14 years) were evaluated. The following biomarkers were used: FT, AST‐to‐platelet ratio index (APRI), Forns index, hyaluronic acid and FibroMeter. We applied a published algorithm suggesting that if FT is in concordance with APRI and/or Forns score, then the FT concurs with liver biopsy for estimation of fibrosis. Concordance of three or more biomarkers was present in 43.2% (57/132) of the patients. This high discordance rate was mainly because of indeterminate scores. Significant fibrosis (F2–F4) was estimated at 34.8% (46/132) and 37.9% (50/132) by the FT and FibroMeter respectively. The discordance rate between the FT and FibroMeter was 16.7% (22/132), (P < 0.01 vs. other biomarkers). Using the algorithm, liver histology could be confidently estimated in 69.7% (92/132) of the patients. Concordance between the FT and FibroMeter in those patients who met the terms of the algorithm was 90.2% (83/92). Discordance between biomarkers is significant, and is mainly because of biomarkers with indeterminate results. The concordance rate between FT and FibroMeter is higher compared with the other biomarkers. Practical combination of tests may potentially limit the need of liver biopsy in the majority of haemophilia patients.
The importance of B‐cells and ecto‐5′nucleotidase in Mycoplasma fermentans infection and the relevance to rheumatoid arthritis
Authors: Johnson Sheena M.
Published: August 2007

The aim of this work was to discover if Mycoplasma fermentans, which is known to infect B cells, could be the cause of the raised ecto‐5′‐nucleotidase observed in the synovial fluid of rheumatoid arthritis patients. The ecto‐5′‐nucleotidase activity in the patients' serum has been shown to correlate with the erythrocyte sedimentation rate and DNA from the mycoplasma has been found in the synovial fluid. B lymphoblastoid cell lines were exposed to 16 strains of Mycoplasma fermentans and their ecto‐5′‐nucleotidase, CD73, was measured both biochemically and by mouse antibodies to human ecto 5′‐nucleotidase using the fluorescence activated cell sorter. The type strain, PG 18, did not grow with the B cells. Some of the mycoplasma strains (9/15) increased the cellular ecto‐5′‐nucleotidase activity from twice to 17 fold, and usually showed 5′‐nucleotidase activity themselves. At least one strain, M106, induced human 5′‐nucleotidase on the normally 5′‐nucleotidase negative Daudi and Raji Burkitt's lymphoma cell lines, and increased sevenfold the 5′‐nucleotidase on the monocyte/macrophage cell line THP‐1. Growing the cells in aged medium increased the level of mycoplasma infection. This mycoplasma‐induced enzyme showed a conformational change and an increase in activity with a glycosylation change involving mannose groups. The other group of strains, mostly of respiratory or cell culture origin, usually did not have any 5′‐nucleotidase of their own and decreased the B‐cell enzyme activity by about half. Electron microscopy and flow cytometry showed that the strain M106 was filamentous and could be found inside the B‐cells. The 5′‐nucleotidase‐inducing strains of M. fermentans may be important in the aetiology of rheumatoid arthritis.
Does interference competition with wolves limit the distribution and abundance of coyotes?
Authors: BERGER KIM MURRAY , GESE ERIC M.
Published: August 2007

Interference competition with wolvesCanis lupusis hypothesized to limit the distribution and abundance of coyotesCanis latrans, and the extirpation of wolves is often invoked to explain the expansion in coyote range throughout much of North America.

We used spatial, seasonal and temporal heterogeneity in wolf distribution and abundance to test the hypothesis that interference competition with wolves limits the distribution and abundance of coyotes. From August 2001 to August 2004, we gathered data on cause‐specific mortality and survival rates of coyotes captured at wolf‐free and wolf‐abundant sites in Grand Teton National Park (GTNP), Wyoming, USA, to determine whether mortality due to wolves is sufficient to reduce coyote densities. We examined whether spatial segregation limits the local distribution of coyotes by evaluating home‐range overlap between resident coyotes and wolves, and by contrasting dispersal rates of transient coyotes captured in wolf‐free and wolf‐abundant areas. Finally, we analysed data on population densities of both species at three study areas across the Greater Yellowstone Ecosystem (GYE) to determine whether an inverse relationship exists between coyote and wolf densities.

Although coyotes were the numerically dominant predator, across the GYE, densities varied spatially and temporally in accordance with wolf abundance. Mean coyote densities were 33% lower at wolf‐abundant sites in GTNP, and densities declined 39% in Yellowstone National Park following wolf reintroduction.

A strong negative relationship between coyote and wolf densities (β = –3·988,P < 0·005,r2 = 0·54,n = 16), both within and across study sites, supports the hypothesis that competition with wolves limits coyote populations.

Overall mortality of coyotes resulting from wolf predation was low, but wolves were responsible for 56% of transient coyote deaths (n = 5). In addition, dispersal rates of transient coyotes captured at wolf‐abundant sites were 117% higher than for transients captured in wolf‐free areas.

Our results support the hypothesis that coyote abundance is limited by competition with wolves, and suggest that differential effects on survival and dispersal rates of transient coyotes are important mechanisms by which wolves reduce coyote densities.
Testing biotic indicator taxa: the sensitivity of insectivorous mammals and their prey to the intensification of lowland agriculture
Authors: Pocock Michael J. O. , Jennings Nancy
Published: August 2007

Changes to agricultural policy aim to extensify agriculture and increase biodiversity. However, it is not known how sensitive many taxa are to intensification. Sensitive taxa could be used as biotic indicators, to assess changes over time and the effectiveness of policy changes.

We sampled shrews, bats and their prey (beetles, flies and moths) on matched pairs of sites and assessed the response in their abundance to aspects of intensification: increased agrochemical inputs (using abundance on matched organic and conventional cereal fields as a proxy), the switch from hay to silage (using abundance on matched hay and silage fields) and boundary loss (using abundance in the field and near the boundary as a proxy, in cereal and grass separately). We quantified the abundance‐derived sensitivity of the taxa in order to assess their use as biotic indicators.

There was substantial variation in the sensitivity of taxa to the three aspects of intensification. Most estimates (51%) of sensitivity to boundary loss were significant, but only 8% for increased agrochemical inputs and 16% for the switch from hay to silage. Sensitivity to one aspect of intensification was not significantly related to sensitivity to another.

Insectivorous mammals were relatively insensitive to increased agrochemical inputs and the switch from hay to silage, but strongly sensitive to boundary loss.

Taxa with significant sensitivity to increased agrochemical inputs included some Carabidae and Diptera. We found fewer significant differences in abundance between organic and conventional farms than previous workers, probably because we controlled for boundary characteristics, suggesting that the quality of field boundaries is important in influencing biodiversity differences between organic and conventional farms.

The switch from hay to silage had a positive effect on some Coleoptera and Diptera but a substantial negative effect on Hepialidae (Lepidoptera).

Synthesis and applications. The recorded sensitivity of taxa to changes in agricultural practices is highly variable. Therefore, the selection of biotic indicator taxa of agricultural intensification is not straightforward. If surveys of biotic indicator taxa are used to assess the effectiveness of changes in agricultural practice, empirical evidence should be used to select suitable taxa.
Sources of knowledge in clinical practice in postgraduate medical students and faculty members: a conceptual map
Authors: Yousefi‐Nooraie Reza , Shakiba Behnam , Mortaz‐Hedjri Soroush , Soroush Ahmad R.
Published: August 2007

Objectives  To determine the most important knowledge sources that can influence clinical practice and to cluster them in conceptual groups based on their relative importance.

Methods  Faculty members, fellows and residents of a large teaching tertiary care hospital were asked to rate the importance of different resources in their daily clinical practice and their understanding of some common terms from evidence‐based medicine. The knowledge sources were distributed in a two‐dimensional map using multidimensional scaling and hierarchical cluster analysis.

Results  A total of 250 of 320 recruited hospital staff returned the questionnaires. The most important resources in daily practice were English journals, text books and literature searching for faculty members, experience, text books and English journals for fellows and text books, experience and peers for residents. Regional journals were the least important resources for all study groups. About 62.7% of residents did not know the meaning of ‘number needed to treat’, 36.8%‘confidence interval’, 54.9%‘confounding factor’ and 44.6%‘meta‐analysis’. The percentages for faculty members were 41.3%, 37%, 42.2% and 39.1%. The knowledge sources were placed in four clusters in a point map derived from the multidimensional scaling process.

Conclusion  The dominance of the traditional information resources and experience‐based medicine debate which is the consequence of traditional approaches to medical education may be one of the considerable barriers to the dissemination of evidence‐based medicine in developing countries. The evidence‐based clinical practice guidelines could be used as a useful passive‐predigested source for busy clinicians to make informed decisions. A considerable Western bias may undermine the local research in developing world.
Evidence‐based practice and determinants of research use in elderly care in Sweden
Authors: Boström Anne‐Marie , Wallin Lars , Nordström Gun
Published: August 2007

Rationale and objective  Evidence‐based practice is a strategic ingredient in today’s health care. Despite extensive efforts to produce and disseminate clinical guidelines, research uptake is still a difficult task. In Sweden, elderly care (EC) has shifted from hospital care to community‐based care, and the major nursing‐staff group in EC has no university education. These and other factors make implementation of evidence‐based care particularly challenging in EC settings. The purpose of this study was to identify determinants of research utilization in EC.

Method  Two questionnaires that cover research utilization and organizational climate were mailed to all staff (n = 132) working in seven EC units. The response rate was 67%.

Results  Of all respondents, 28% reported that they used research findings in daily practice (the RU group). Remaining respondents constituted the non‐RU group. Significant differences existed between the RU group and the non‐RU group as per six individual and six organizational factors. Using logistic regression models, four factors were significantly related to research utilization, namely: attitudes toward research (OR = 5.52, P = 0.004); seeking research that is related to clinical practice (OR = 5.56, P = 0.019); support from unit manager (OR = 4.03, P = 0.044) and access to research findings at work place (OR = 6.65, P = 0.005).

Conclusions  Individual and organizational factors were associated with the use of research in EC. Despite distinguishing conditions in EC settings, identified factors reflect well‐known determinants of research use that, as in many other health care contexts, should be considered in the endeavours of evidence‐based practice.
The challenge of using the low back pain guidelines: a qualitative research
Authors: Dahan Rachel , Borkan Jeffry , Brown Judith‐Bell , Reis Shmuel , Hermoni Doron , Harris Stewart
Published: August 2007

Purpose  Current low back pain (LBP) clinical guidelines have helped to summarize the scientific evidence and research, but have failed to provide tools and guide family physicians (FPs). The purpose of this study is to identify barriers and facilitators for the implementation of LBP guidelines from family FPs’ perspective.

Methods  A qualitative focus group study of FPs in the north of Israel. Purposeful sampling was used to recruit participants, all of them board‐certified FPs. Four focus groups were created, and discussions were taped, transcribed and analysed for major themes.

Results  Focus groups findings have expanded the understanding of the intellectual and mental challenges faced by Israeli FPs caring for LBP patients and highlighted the many obstacles to implementing LBP guidelines. Physicians’ decision‐making, pertaining to LBP, functions on three levels simultaneously: the physicians’ agenda based on familiarity with the guidelines; their need to remain grounded in the context of the specific patient–doctor relationship; and the constraints and demands of the physician’s workplace, medical system and environment.

Conclusions  Despite an overall positive attitude towards LBP guideline implementation, FPs found it hard to come to terms with the conflicting dimensions of LBP patient care. The patient–doctor interaction determined the outcome of the encounter, whether it complied with the guidelines and whether the encounter leads to a healing process or to a vicious circle of unnecessary utilization of services.
Incidence, types and characteristics of aggressive behaviour in treatment facilities for adults with mild intellectual disability and severe challenging behaviour
Authors: Tenneij N. H. , Koot H. M.
Published: August 2007

Background Inpatient aggression in treatment facilities for persons with intellectual disability (ID) can have aversive consequences, for co‐clients and staff, but also for the aggressors themselves. To manage and eventually prevent inpatient aggressive incidents, more knowledge about their types and characteristics is necessary.

Method In four facilities, totalling 150 beds, specialized in the treatment of adults with mild ID or severe challenging behaviour, aggressive incidents were registered during 20 weeks using the Staff Observation Aggression Scale‐Revised. Characteristics of auto‐aggressive and outwardly directed incidents and differences in their incidence in male and female clients in these facilities were compared.

Results During the observation period of 20 weeks, 639 aggressive incidents were documented. Most of these (71%) were outwardly directed, predominantly towards staff, while most of the remaining incidents were of an auto‐aggressive nature. Of the 185 clients present during the observation period, 44% were involved in outwardly directed incidents (range per client 1–34), and 12% in auto‐aggressive incidents (range per client 1–92). Auto‐aggressive and outwardly directed incidents differed regarding source of provocation, means used during the incident, consequences of the incident and measures taken to stop the incident. The proportion of men and women involved in each type of incident was comparable, as well as the majority of the characteristics of outwardly directed incidents caused by men and women.

Conclusions Although approximately half of all clients were involved in aggressive incidents, a small minority of clients were responsible for the majority of incidents. Therefore, better management and prevention of aggressive incidents for only a small group of clients could result in a considerable overall reduction of aggressive incidents in treatment facilities. Comparability of aggressive behaviour in these facilities shown by men and women and differences in characteristics of auto‐aggressive and outwardly directed incidents are discussed.