bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of IL-10 producing CD4+ T cells with regulatory activities by stimulation with IL-10 gene-modified bone marrow derived dendritic cells
Authors: Fu C-L , Chuang Y-H , Huang H-Y , Chiang B-L
Published: October 2008

Dendritic cells (DCs) can induce both tolergenic as well as effective immune responses in the lung. Pulmonary DCs producing interleukin (IL)-10 mediated tolerance induced by respiratory exposure to antigen. IL-10 is an important immunosuppressive cytokine, which inhibits maturation and function of DC. To assess whether IL-10 producing DCs can exert the tolergenic effect through the differentiation of regulatory T cells, bone marrow derived DCs were genetically modified by IL-10 expressing adenovirus. IL-10 gene modified DCs (Ad-IL-10-DC) displayed a characteristic phenotype of immature DCs. Here we showed that in vitro repetitive stimulation of naïve DO11·10 CD4+ T cells with Ad-IL-10-DCs resulted in a development of IL-10 producing T-cell regulatory cells. These T cells could not proliferate well but also lost their ability to produce interferon-γ upon restimulation with irradiated splenocytes and ovalbumin peptide. Furthermore, in co-culture experiments these T cells inhibited the antigen-driven proliferation of naïve CD4+ T cells in a dose-dependent manner. Our findings demonstrated that IL-10 producing DCs had the potential to induce the differentiation of Tr1-like cells and suggested their therapeutic use.
Essential role of toxin A in C. difficile 027 and reference strain supernatant-mediated disruption of Caco-2 intestinal epithelial barrier function
Authors: Sutton P A , Li S , Webb J , Solomon K , Brazier J , Mahida Y R
Published: October 2008

Clostridium difficile induces mucosal inflammation via secreted toxins A and B and initial interactions between the toxins and intestinal epithelial cells (which lead to loss of barrier function) are believed to be important in disease pathogenesis. Secreted toxin-specific antibodies may inhibit such interactions. Using the Caco-2 epithelial cell line, we have investigated the use of an anti-toxin A monoclonal antibody (ATAA) in providing protection against toxin A-mediated disruption of epithelial barrier function (assessed by measurement of transepithelial electrical resistance and luminal to basolateral flux of labelled dextran). In contrast to free antibody, ATAA conjugated to sepharose beads was more effective in neutralizing the activity of purified toxin A. Sepharose bead-conjugated ATAA was subsequently used to investigate the contribution of toxin A in epithelial injury mediated by C. difficile supernatant samples (containing toxins A, B and other products). Loss of barrier function mediated by apical application of supernatant samples of reference and epidemic 027 strains of C. difficile was abrogated by neutralization of toxin A. However, this was not the case when the supernatant samples were applied to the basal surface of epithelial monolayers. In conclusion, our studies have shown that (i) sepharose bead-conjugated ATAA is more effective in neutralizing toxin A than free antibody and (ii) when the apical (luminal) surface of epithelial monolayers is exposed to the secretory products of reference and 027 strains of C. difficile, toxin A is required for the initial injury that leads to loss of barrier function.
Protein biochip array technology for cytokine profiling predicts etanercept responsiveness in rheumatoid arthritis
Authors: Fabre S , Dupuy A M , Dossat N , Guisset C , Cohen J D , Cristol J P , Daures J P , Jorgensen C
Published: October 2008

In rheumatoid arthritis (RA) there are currently no useful indicators to predict a clinical response to tumour necrosis factor-α (TNF-α) blockade. The purpose of this study was to determine the role of peripheral blood cytokine profiling in differentiating between a good versus poor response to etanercept in RA. Peripheral blood samples were collected at baseline and at 3 months from 33 patients with active disease who were treated twice weekly by etanercept therapy. Responders are defined by the presence of three of four American College of Rheumatology criteria: ≥20% decrease in C-reactive protein (CRP), visual analogue score of disease activity, erythrocyte sedimentation rate and improvement of the disease activity score (28; four values) by ≥1·2 obtained at 3 months. Twelve cytokines were measured from serum collected on days 0 and 90 by proteomic array (protein biochip array, Investigator Evidence, Randox France), including interleukin (IL)-6, TNF-α, IL-1a, IL-1b, IL-2, IL-8, interferon-γ, IL-4, IL-10, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF) and vascular endothelium growth factor. Our results showed that high serum levels of MCP-1 and EGF were associated with a response to etanercept. In addition, the increase of two combined parameters CRP and EGF was predictive of a response to etanercept treatment at 3 months (sensitivity: 87·5% and specificity: 75%, accuracy: 84·4%). These findings suggest that cytokine profiling by proteomic analysis before treatment initiation may help to identify a responder patient to TNF-α blocking agents in RA.
Immunity andToxoplasmaretinochoroiditis
Authors: Wallace G R , Stanford M R
Published: October 2008

Toxoplasma infection accounts for up to 50% of all cases of posterior uveitis worldwide. In this review the control of Toxoplasma infection generally, and specific in the eye, by the immune system is discussed.
An approach to the patient with urticaria
Authors: Deacock S J
Published: October 2008

Patients with urticaria make up a large proportion of the referrals to allergy clinics. There are many causes of urticaria and it is the clinical history which is most important when attempting to identify potential causes; however, urticaria is very often idiopathic. In a small minority of patients urticaria may be a symptom of a serious underlying medical illness or the allergic symptoms may progress to cause systemic reactions, and it is important to identify these patients and to remember that severe urticaria is a distressing and disabling condition. This review will discuss classification, investigation and treatment of urticaria and will consider some of the more unusual types of urticaria that may be encountered in the out-patient clinic.
Clinical Immunology Review Series: An approach to the patient with anaphylaxis
Authors: El-Shanawany T , Williams P E , Jolles S
Published: October 2008

Anaphylaxis is a severe, life-threatening, generalized or systemic hypersensitivity reaction. While there is agreement as to this definition of anaphylaxis, the clinical presentation is often variable and it is not uncommon for there to be debate after the event as to whether anaphylaxis had actually occurred. The management of anaphylaxis falls into two distinct phases: (1) emergency treatment and resuscitation of a patient with acute anaphylaxis and (2) the search for a cause for the event and the formulation of a plan to prevent and treat possible further episodes of anaphylaxis. Both aspects are important in preventing death from anaphylaxis and are covered in this review.
Clinical Immunology Review Series: An approach to the use of the immunology laboratory in the diagnosis of clinical allergy
Authors: Williams P , Sewell W A C , Bunn C , Pumphrey R , Read G , Jolles S
Published: October 2008

In the last 10 years UK immunology laboratories have seen a dramatic increase in the number and range of allergy tests performed. The reasons for this have been an increase in the incidence of immunoglobulin E (IgE)-mediated allergic disease set against a background of greater public awareness and more referrals for assessment. Laboratory testing forms an integral part of a comprehensive allergy service and physicians treating patients with allergic disease need to have an up-to-date knowledge of the range of tests available, their performance parameters and interpretation as well as the accreditation status of the laboratory to which tests are being sent. The aim of this review is to describe the role of the immunology laboratory in the assessment of patients with IgE-mediated allergic disease and provide an up-to-date summary of the tests currently available, their sensitivity, specificity, interpretation and areas of future development.
Dehydroepiandrosterone and metformin regulate proliferation of murine T lymphocytes
Authors: Solano M E , Sander V , Wald M R , Motta A B
Published: October 2008

The aim of the present study was to assess the effect of dehydroepiandrosterone (DHEA: 10 µM) and metformin (10 µM and 100 µM) in regulating proliferation of cultured T lymphocytes. T cells were isolated from lymph nodes of prepuberal BALB/c mice. We found that DHEA, metformin and DHEA + metformin added to the incubation media diminished proliferation of T cells. The inhibition by DHEA was higher than that produced by metformin, while the combined treatment showed a synergistic action that allowed us to speculate distinct regulatory pathways. This was supported later by other findings in which the addition of DHEA to the incubation media did not modify T lymphocyte viability, while treatment with metformin and DHEA + metformin diminished cellular viability and increased both early and late apoptosis. Moreover, DHEA diminished the content of the anti-oxidant molecule glutathione (GSH), whereas M and DHEA + metformin increased GSH levels and diminished lipid peroxidation. We conclude that DHEA and metformin diminish proliferation of T cells through different pathways and that not only the increase, but also the decrease of oxidative stress inhibited proliferation of T cells, i.e. a minimal status of oxidative stress, is necessary to trigger cellular response.
Renal damage and death in weaned mice after oral infection with Shiga toxin 2-producing Escherichia coli strains
Authors: Brando R J F , Miliwebsky E , Bentancor L , Deza N , Baschkier A , Ramos M V , Fernández G C , Meiss R , Rivas M , Palermo M S
Published: October 2008

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infections are considered a public health problem in both developed and developing countries because of their increasing incidence and the severity of clinical presentation. Approximately 10% of infected patients develop complications such as haemolytic uraemic syndrome (HUS) characterized by acute renal failure, thrombocytopenia and haemolytic anaemia. The precise sequence of events leading to HUS is still understood incompletely. Because of the lack of a reproducible small animal model for EHEC infections, in vivo studies examining EHEC–host early interactions are limited and insufficient. The aim of this study was to characterize the weaned BALB/c mouse as a model of E. coli O157:H7 infection. In this paper we report that human Shiga toxin 2 (Stx2)-producing EHEC strains can adhere to the intestinal epithelium of weaned BALB/c mice, and produce local damage which leads to systemic disease and death in a percentage of infected mice. The lethality of the EHEC strain is closely age-dependent, and is related to the bacterial ability to colonize intestine and to produce Stx2. It can be concluded that the weaned BALB/c mouse can be used as a small animal model to study host early responses, and the role of bacterial pathogenic factors in the induction of systemic disease, thus providing a useful tool for the evaluation of therapeutic or vaccine approaches.
Detailed analysis of Epstein–Barr virus-specific CD4+ and CD8+ T cell responses during infectious mononucleosis
Authors: Scherrenburg J , Piriou E R W A N , Nanlohy N M , van Baarle D
Published: October 2008

We studied simultaneously Epstein–Barr virus (EBV)-specific CD4+ and CD8+ T cell responses during and after infectious mononucleosis (IM), using a previously described 12-day stimulation protocol with EBNA1 or BZLF1 peptide pools. Effector function of EBV-specific T cells was determined after restimulation by measuring intracellular interferon-γ production. During IM, BZLF1-specifc CD4+ T cell responses were dominant compared with CD8+ T cell responses. EBNA1-specific CD4+ and CD8+ T cell responses were low and remained similar for 6 months. However, 6 months after IM, BZLF1-specific CD4+ T cell responses had declined, but CD8+ T cell responses had increased. At diagnosis, EBV-specific CD8+ T cells as studied by human leucocyte antigen class I tetramer staining comprised a tetramerbrightCD8bright population consisting mainly of CD27+ memory T cells and a tetramerdimCD8dim population consisting primarily of CD27- effector T cells. The remaining EBV-specific CD8+ T cell population 6 months after the diagnosis of IM consisted mainly of tetramerbrightCD8brightCD27+ T cells, suggesting preferential preservation of memory T cells after contraction of the EBV-specific T cell pool.
Translational Mini-Review Series on the Immunogenetics of Gut Disease: Immunogenetics of coeliac disease
Authors: Dubois P C , van Heel D A
Published: October 2008

OTHER ARTICLE PUBLISHED IN THIS TRANSLATIONAL MINI-REVIEW SERIES ON THE IMMUNOGENETICS OF GUT DISEASE

Immunogenetics of Inflammatory Bowel Disease

Recent advances in immunological and genetic research in coeliac disease provide new and complementary insights into the immune response driving this chronic intestinal inflammatory disorder. Both approaches confirm the central importance of T cell-mediated immune responses to disease pathogenesis and have further begun to highlight other relevant components of the mucosal immune system, including innate immunity and the control of lymphocyte trafficking to the mucosa. In the last year, the first genome wide association study in celiac disease led to the identification of multiple new risk variants. These risk regions implicate genes involved in the immune system. Overlap with autoimmune diseases is striking with several of these regions being shown to confer susceptibility to other chronic immune-mediated diseases, particularly type 1 diabetes.
Impaired CD4+ and CD8+ T cell phenotype and reduced chemokine secretion in recent-onset type 1 diabetic children
Authors: Hedman M , Faresjö M , Axelsson S , Ludvigsson J , Casas R
Published: October 2008

Although the role of the T cell-mediated autoimmune reaction in type 1 diabetes (T1D) is conclusive, studies including data from human circulating CD4+ and CD8+ lymphocytes subsets during the disease onset and posterior development are scarce. Further, chemokines and chemokine receptors are key players in the migration of pathogenic T cells into the islets of non-obese diabetic mice developing T1D, but few studies have investigated these markers in human T1D patients. We studied the expression of T helper 1 (Th1)- and Th2-associated chemokine receptors, and the two isoforms of CD45 leucocyte antigen on CD4+ and CD8+ lymphocytes from T1D and healthy children, as well as the secretion of chemokines in cell supernatants in peripheral blood mononuclear cells. Our results showed increased expression of CCR7 and CD45RA and reduced CD45RO on CD8+ cells among recent-onset T1D patients. The percentages of CD4+ cells expressing CXC chemokine receptor 3 (CXCR3), CXCR6 and CCR5, and the secretion of interferon-γ-induced protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1α and MIP-1β was lower among diabetics. Low expression of Th1-associated receptors and secretion of chemokines, together with an increased amount of CD8+ cells expressing CD45RA and CCR7 in T1D patients therefore might represent suboptimal Th function in T1D, leading to impaired T cytotoxic responses or alternatively reflect a selective recruitment of Th1 cells into the pancreas.
Mitogenic effect contributes to increased virulence ofStreptococcus suissequence type 7 to cause streptococcal toxic shock-like syndrome
Authors: Zheng H , Ye C , Segura M , Gottschalk M , Xu J
Published: October 2008

Streptococcus suis serotype 2 sequence type 7 strains emerged in 1996 and caused a streptococcal toxic shock-like syndrome in 1998 and 2005 in China. Evidence indicated that the virulence of S. suis sequence type 7 had increased, but the mechanism was unknown. The sequence type 7 strain SC84, isolated from a patient with streptococcal toxic shock-like syndrome during the Sichuan outbreak, and the sequence type 1 strain 31533, a typical highly pathogenic strain isolated from a diseased pig, were used in comparative studies. In this study we show the mechanisms underlying cytokine production differed between the two types of strains. The S. suis sequence type 7 strain SC84 possesses a stronger capacity to stimulate T cells, naive T cells and peripheral blood mononuclear cell proliferation than does S. suis sequence type 1 strain 31533. The T cell response to both strains was dependent upon the presence of antigen-presenting cells. Histo-incompatible antigen-presenting cells were sufficient to provide the accessory signals to naive T cell stimulated by the two strains, indicating that both sequence type 7 and 1 strains possess mitogens; however, the mitogenic effect was different. Therefore, we propose that the difference in the mitogenic effect of sequence type 7 strain SC84 compared with the sequence type 1 strain 31533 of S. suis may be associated with the clinical, epidemiological and microbiological difference, where the ST 7 strains have a larger mitogenic effect.
Macrophage activation, phagocytosis and intracellular calcium oscillations induced by scorpion toxins fromTityus serrulatus
Authors: Petricevich V L , Reynaud E , Cruz A H , Possani L D
Published: October 2008

The research described here is focused upon studying the activation of mice peritoneal macrophages when submitted to in vitro effects of Tityus serrulatus scorpion venom and its major toxic peptides. Several functional events were analysed, such as: cytotoxicity, spreading, extent of phagocytosis, vacuole formation and changes of internal calcium concentration. Among the main results observed, when macrophages are subjected to the effects of soluble venom of Tityus serrulatus scorpion venom, a partially purified fraction (FII) or a pure toxin (Ts1), are an increment in the percentage of phagocytosis and vacuole formation, a decrement of the spreading ability, accompanied by oscillations of internal calcium concentration. The net results demonstrate that scorpion venom or its major toxins are effective stimulators of macrophage activity; the effect of whole soluble venom or partially purified fractions is due to the toxic peptides, seen here clearly with Ts1. The possible involvement of Na+-channels in these events is discussed. A basic understanding of the underlying molecular mechanisms responsible for macrophage activation should serve as a foundation for novel drug development aimed at modulating macrophage activity.
Nitric oxide attenuates vascular endothelial cadherin-mediated vascular integrity in human chronic inflammation
Authors: Hama S , Takeichi O , Fujisaki K , Tanabe N , Maeno M , Ochiai K
Published: October 2008

In this study, we examined the role of nitric oxide (NO) in controlling vascular integrity mediated by vascular endothelial (VE)-cadherin in chronic inflammation. Periapical granulomas were analysed for the expression of inducible NO synthase (iNOS) and VE-cadherin, and more iNOS expression than VE-cadherin was shown. Human umbilical vein endothelial cells (HUVECs) were stimulated with proinflammatory cytokines and lipopolysaccharide extracted from Porphyromonas gingivalis and it induced iNOS expression, whereas it reduced VE-cadherin expression, compared with negative controls. On the other hand, pre-incubation with 1400W, an iNOS-specific inhibitor, markedly reduced iNOS expression in stimulated HUVECs and restored VE-cadherin expression to its control level, suggesting that vascular integrity was modulated in conjunction with the reduction of NO. Immunocytochemistry confirmed the functional role of NO in cultured HUVEC monolayers with or without 1400W. These data are consistent with a hypothesis suggesting that NO could attenuate VE-cadherin-mediated vascular integrity in human chronic inflammation.
Tissue mRNA expression of the glucocorticoid receptor and its splice variants in fatal critical illness
Authors: Peeters R. P. , Hagendorf A. , Vanhorebeek I. , Visser T. J. , Klootwijk W. , Mesotten D. , Wouters P. J. , Koper J. W. , De Jong F. H. , Feelders R. A. , Lamberts S. W. J. , Van den Berghe G.
Published: October 2008

Background  Critical illness results in activation of the hypothalamic–pituitary–adrenal (HPA) axis, which might be accompanied by a peripheral adaptation in glucocorticoid sensitivity. Tissue sensitivity is determined by the active glucocorticoid receptor GRα, of which two splice variants involving the hormone‐binding domain exist, GRβ and GR‐P.

Objective  To study tissue mRNA expression of the GR and its splice variants in fatal critical illness.

Design and methods  We assessed mRNA expression of the GRα, GRβ and GR‐P variants in liver (n = 58) and muscle (n = 65) of patients who had died after intensive care, and had been randomized for insulin treatment. We analysed whether GR mRNA expression was associated with insulin treatment, cortisol levels and glucocorticoid treatment.

Results  GRα and GR‐P mRNA constituted 87 ± 8% and 13 ± 2%, respectively, of total GR mRNA in liver. GRβ mRNA could only be amplified in five liver samples. All variants were present in most muscle samples (α = 96 ± 11%, P = 3·9 ± 0·4%, β = 0·010 ± 0·002%). GR expression was not associated with insulin therapy. A strong positive relationship was observed between the different GR variants in both liver and muscle (P < 0·001 for all). Serum cortisol levels were negatively associated with liver GRα and muscle GR‐P expression (P < 0·05). mRNA expression of both liver GRα and GR‐P, but not muscle GR, was substantially lower in patients who had received exogenous glucocorticoids (P < 0·01).

Conclusion  We demonstrate the presence of GRα and GR‐P mRNA in liver and of GRα, GRβ and GR‐P mRNA in muscle, with no evidence for altered splicing in critical illness. In contrast to muscle GR, liver GR expression was substantially lower in patients receiving exogenous glucocorticoids.
Cerebral white matter hyperintensity is mainly associated with hypertension among the components of metabolic syndrome in Koreans
Authors: Choi Hoon Sung , Cho Young Min , Kang Jin Hwa , Shin Chan Soo , Park Kyong Soo , Lee Hong Kyu
Published: October 2008

Background Cerebral white matter hyperintensity (WMH) is a common abnormality in brain magnetic resonance imaging (MRI) and is known to be associated with ischaemic stroke. Previous studies revealed that the risk factors for cerebral WMH were age, female gender, hypertension and diabetes. In this study we examined the association between cerebral WMH and metabolic syndrome, a cluster of hypertension, glucose intolerance, abdominal obesity and dyslipidaemia.

Methods and results We reviewed the results of brain MRI of 5498 subjects who underwent routine check‐ups including laboratory tests at the Seoul National University Health Care System. Among the subjects who met the inclusion criteria (n = 5104), 1693 (33·2%) had cerebral WMH. They were characterized by old age, female predominance, higher body mass index (BMI), larger waist circumference, higher blood pressure, higher fasting plasma glucose level, and higher haemoglobin A1c (HbA1c). In multivariate analyses, age, female gender and hypertension were the independent risk factors for cerebral WMH. Metabolic syndrome was associated with cerebral WMH after adjusting for age and gender [odds ratio (OR) 1·20, 95% confidence interval (CI) 1·04–1·39,P = 0·014]. Among the components of metabolic syndrome, hypertension was independently associated with cerebral WMH (OR 1·20, 95% CI 1·05–1·38,P = 0·007).

Conclusion Age, female gender and hypertension were risk factors for cerebral WMH in the Korean population. Cerebral WMH was also associated with metabolic syndrome; however, metabolic syndrome offered no advantage over hypertension alone in predicting cerebral WMH.
Risk factors for cardiovascular disease do not fully explain differences in carotid intima–media thickness between Indigenous and European Australians without diabetes
Authors: Maple‐Brown L. , Hodge A. , Cunningham J. , Celermajer D. S. , O'Dea K.
Published: October 2008

Objective  To investigate whether cardiovascular risk factors can explain the higher carotid intima–media thickness (CIMT) in Indigenous compared with European Australians.

Design  Cross‐sectional study in three subgroups.

Patients  Non‐diabetic urban European (n = 86), urban Indigenous (n = 69), and remote Indigenous (n = 60) Australians aged 25–64 years.

Measurements  CIMT, age, sex, anthropometry, blood pressure, smoking status, fasting glucose and insulin, haemoglobin (Hb)A1c, homocysteine, C‐reactive protein (CRP), lipids, urinary albumin and creatinine.

Results  CIMT and levels of risk factors, except fasting glucose and total cholesterol, worsened across the three groups. Logn fasting insulin [β = 0·022, 95% confidence interval (CI) 0–0·0439], age (β = 0·006, 95% CI 0·004–0·007), gender (female β = –0·005 vs. male, 95% CI –0·084 to –0·026), mean arterial pressure (MAP) (β = 0·001, 95% CI 0·001–0·002) and ethnicity/location [urban Indigenous (β = 0·027, 95% CI –0·010 to 0·064 vs. European); remote Indigenous (β = 0·083, 95% CI 0·042–0·123 vs. European)] explained 41% of variance in CIMT. Significant interactions were seen for ethnicity/location with age (P = 0·014) and MAP (P = 0·018). Age was consistently associated with CIMT across the three populations, and was associated with larger increments in CIMT for the Indigenous subgroups (β = 0·007, 95% CI 0·005–0·009 urban; β = 0·007, 95% CI 0·004–0·010 remote) compared with Europeans (β = 0·003, 95% CI 0·002–0·006) in models including age, sex and MAP. MAP was only associated with CIMT in the remote Indigenous subgroup.

Conclusion  After adjusting for selected risk factors, CIMT in remote Indigenous participants was still higher than in Europeans. The slope of the association between age and CIMT steepened from urban Europeans to remote Indigenous.
Puberty induction in Turner syndrome: results of oestrogen treatment on development of secondary sexual characteristics, uterine dimensions and serum hormone levels
Authors: Bannink E. M. N. , Van Sassen C. , Van Buuren S. , De Jong F. H. , Lequin M. , Mulder P. G. H. , De Muinck Keizer‐Schrama S. M. P. F.
Published: October 2008

Background  Besides short stature, gonadal dysgenesis leading to a lack of oestrogen is one of the main characteristics of Turner syndrome (TS). In most TS girls, puberty is induced with exogenous oestrogens.

Objective  To describe the pubertal development and uterine dimensions achieved by low‐dose 17β‐oestradiol (17β‐E2) orally started at an appropriate age. Additionally, to determine whether serum hormone levels aid evaluation of pubertal progression.

Design  In 56 TS girls, we prospectively studied pubertal stage, serum E2, LH, FSH, SHBG and oestrone (E1), starting oestrogen treatment with a low‐dose 17β‐E2 (5 µg/kg/day) during GH treatment at mean (SD) age 12·7 (0·7) years. Hormone levels were measured at start, 3 months after start and after increasing 17β‐E2 dosage. Uterine dimensions were measured in 39 TS women at age 19·9 (2·2) years.

Results  Although breast and pubic hair development were similar to that in normal Dutch girls up to Tanner stage B5 and P5, respectively, breast development was 2 years later. Before oestrogen therapy, E2 levels were comparable to those in prepubertal girls. With a 17β‐E2 dose of 5 µg/kg/day, these levels increased significantly, becoming comparable to normal late pubertal or adult concentrations, whereas SHBG levels were unchanged. At the adult 17β‐E2 dose, SHBG had increased significantly. Uterus shape was juvenile in four (10·2%), cylindrical in four and mature‐adult shaped in 31 (79·5%) of TS patients.

Conclusions  During GH treatment in TS girls, normal breast development up to B5 can be mimicked, with just a 2‐year delay. In a clinical setting, serum hormone levels provide no additional information for evaluating pubertal progression. After age‐appropriate pubertal induction, uterine dimensions in women aged nearly 20 years were subnormal. It remains unclear whether this was related to E2 dosage, timing or duration, or factors related to TS.
Seasonal mortality trends in tree‐feeding insects: a field experiment
Authors: REMMEL TRIINU , TAMMARU TOOMAS , MÄGI MARKO
Published: October 2008

Abstract 1. The majority of general life‐history models treat the environment as being invariable through time, even though temporal variation in selective agents could dramatically change the outcomes, e.g. in terms of optimal size and time at maturity. For herbivorous insects, seasonal differences in food quality are reasonably well described, but seasonal dynamics of top‐down selective forces are poorly documented.

2. The present study attempted to quantify seasonal changes in predation risk of folivorous insect larvae in temperate forest habitats. In a series of field experiments, artificial larvae were exposed to predators, and the resulting bird‐inflicted damage was recorded. The trials were repeated regularly throughout the course of two summers.

3. A distinct peak of larval mortality was recorded in mid‐June (the nestling period for most insectivorous passerine birds), after which predation risk declined to a plateau of 20–30% below the peak value.

4. The recorded pattern is interpreted as a consequence of seasonal changes in the number and behaviour of insectivorous birds, and the abundance of alternative food resources for these predators.

5. A quantitative analysis based on field data indicated that considering temporal variation in mortality in life‐history models is crucial for obtaining realistic predictions concerning central life‐history traits, such as final body size in different generations.
Illness consequences after myocardial infarction: problems with physical functioning and return to work
Authors: Brink Eva , Brändström Yvonne , Cliffordsson Christina , Herlitz Johan , Karlson Björn W.
Published: October 2008

Aim.  This paper is a report of a study to explore health problems, physical and mental functioning, and physical activity in working‐age patients after myocardial infarction, in order to assess the possible effects of these factors on return to work.

Background.  A diagnosis of myocardial infarction may discourage patients from continuing an active working life. Enabling myocardial infarction patients to return to work has benefits for both individuals and society.

Methods.  A convenience sample was recruited of 88 patients, ≤65 years of age, who had suffered a myocardial infarction. Assessments of employment, health‐related quality of life and physical activity (footsteps per day) were conducted in 2005–2006, 4–6 months after myocardial infarction. To explore data and compare groups, t‐tests were applied. Logistic regression analyses were performed to identify variables that best predicted return to work.

Results.  Differences were identified between individuals who were employed after myocardial infarction and those who were not. Those not in work scored lower on variables related to the physical dimension of health‐related quality of life and on physical activity. Logistic regression revealed that a multivariate model including age, physical dimension of health‐related quality of life and footsteps per day predicted return to work in 68% of all cases (R2 = 0·344).

Conclusion.  Low physical health and low physical activity after myocardial infarction negatively affect returning to work. These findings stress the importance of clinical assessment of myocardial infarction patients’ daily physical activity and physical functioning.
Development and testing of four instruments to assess prior conditions that influence nurses' adoption of evidence‐based pain management practices
Authors: Carlson Cathy
Published: October 2008

Aim.  This paper is a report of the development and testing of the psychometric properties of a set of four instruments measuring prior conditions influencing nurses’ decisions to adopt evidence‐based pain management practices.

Background.  Nurses do not use evidence‐based pain management practices consistently. Their adoption of pain management practices depends on several prior conditions. Prior conditions are factors that influence the need to learn more about an innovation and begin the adoption process.

Method.  Four instruments were developed, collectively known as Carlson’s Prior Conditions Instruments, to assess the four theoretically‐derived prior conditions of previous practice, felt needs/problems, innovativeness and norms of the social system that influence nurses’ decisions to adopt evidence‐based pain management practices. Item‐to‐total correlations and Cronbach’s alpha were used to determine internal consistency reliability. Construct validity was examined through principal components factor analysis with varimax rotation. Data were collected as part of a larger study in 2005.

Results.  Content validity of the four instruments was supported through review by experts. The instruments were distributed to nurses (n = 187). Each instrument demonstrated internal consistency (alpha range = 0·731–0·825). Factor analysis demonstrated that the Felt Needs/Problems and Norms of the Social System Instruments were unidimensional, with six and seven items respectively. The Previous Practice Instrument (11 items, three factors) and Innovativeness Instrument (six items, two factors) were multidimensional.

Conclusion.  Initial psychometric testing revealed adequate estimates of reliability and validity for Carlson’s Prior Conditions Instruments. Further research is needed using the tools with nurses in different countries and cultures to test and confirm the constructs.
Erratum et addendum: transient amplification and attenuation in stage‐structured population dynamics
Authors: Townley Stuart , Hodgson David J.
Published: October 2008

Not all members of natural populations contribute equally to population growth or decline. Populations that are disturbed away from stable stage structure will amplify (i.e. get bigger than expected) and/or attenuate (i.e. get smaller than expected) in the short term.

We provide mathematical bounds for the magnitude of this amplification and attenuation, both in terms of absolute population change and population change relative to the long‐term rate of population increase.

Our results correct an important error in an earlier analysis of transient population amplification, and provide new transient bounds for the analysis of population attenuation.

Synthesis and applications. Bounds on transient amplification and attenuation help population managers to gauge ‘worst case’ and ‘best case’ scenarios for the response of stage‐structured populations to disturbance and management strategies. Such bounds help to create an envelope of possible future population scenarios around the mean, long‐term predictions made by eigenvalues and eigenvectors of projection matrix models. Transient amplification, caused by stage structures biased towards reactive life stages, may be exploited by conservation managers wishing to boost population densities in the short term and may be avoided in pest species by stage‐specific control strategies. Similarly, transient attenuation should be avoided by conservation managers and exploited by pest managers.
Misconceived and maladaptive beliefs about heart disease: a comparison between Taiwan and Britain
Authors: Lin Yu‐Ping , Furze Gill , Spilsbury Karen , Lewin Robert JP
Published: October 2008

Aims and objectives.  To assess and compare misconceived and maladaptive beliefs about coronary heart disease between Taiwanese and British people with heart disease.

Background.  Holding misconceived and maladaptive beliefs about heart disease has deleterious effects on a patient’s quality of life. Cultural contexts influence a person’s responses to illness, but little information exists about the ways in which cultural values influence a person’s attributions and coping behaviours regarding their heart disease.

Design.  A cross‐sectional survey using a descriptive comparative design was carried out in Taiwan and Britain.

Methods.  A structured questionnaire was used to elicit misconceived or potentially maladaptive beliefs about heart disease. People with a confirmed diagnosis of coronary heart disease were recruited from a teaching hospital in Taipei (n = 238) and a tertiary cardiothoracic centre in the North of England (n = 204).

Results.  Taiwanese patients held more misconceived and maladaptive beliefs about heart disease than those in Britain. Both British and Taiwanese patients showed high agreement on ‘stress is one of the main causes of heart disease’ and ‘always avoid stress’, but these beliefs were more common in Taiwanese patients (p < 0·001). Misconceptions about avoiding anything that might bring on angina were common in both countries.

Conclusions.  While there were some similarities in the cardiac beliefs held by the two groups of patients, Taiwanese patients held significantly more misconceptions. This may be explained by differences between the patients’ cultures, including social norms, health care provision and health information from the media.

Relevance to clinical practice.  Interventions should be developed to dispel maladaptive beliefs thereby altering the coping actions of patients. The meaning and purpose of specific behaviours needs to be interpreted within the context of a patient’s culture. Awareness of cultural perspectives may help to develop nursing care plans that are more successful as they are more individually applicable to patients.
Use of non‐conventional nurses’ attire in a paediatric hospital: a quasi‐experimental study
Authors: Festini Filippo , Occhipinti Valentina , Cocco Margherita , Biermann Klaus , Neri Stella , Giannini Chiara , Galici Valeria , De Martino Maurizio , Caprilli Simona
Published: October 2008

Aims:  To test the impact of a multi‐coloured non‐conventional attire on a population of children admitted to a paediatric hospital.

Design:  Quasi‐experimental before‐after controlled study.

Background:  It has been suggested that non‐conventional nurses’ uniforms in paediatric settings may contribute to lowering children’s distrust towards healthcare providers and reduce fear. Little formal research has investigated on the impact of nursing attire in a paediatric setting. No study has so far analysed the effects in actual use of a non‐conventional, other than the traditional type of uniform, on a paediatric hospitalised population.

Design:  A quasi‐experimental study.

Methods:  We introduced multi‐coloured nurses’ attire in two wards of a paediatric hospital. Using open questions and semantic differential scales (SDS), we evaluated the effects of this non‐conventional attire on a group of hospitalised children, compared to sex‐and‐age‐matched controls interviewed before the introduction. Parents were also interviewed.

Results:  One hundred and twelve hospitalised children and their parents (n = 112) were studied. The percentage of positive words used by children to define their nurse was higher in children interviewed after the introduction of non‐conventional uniforms (96·2% vs. 81·8%, p = 0·01). Children’s perception of nurses was significantly improved by the use of multi‐coloured attire (‘bad’–‘good’ SDS: p = 0·01; ‘disagreeable’–‘nice’ SDS: p = 0·001). Children’s perceptions regarding hospital environment did not change. Parents’ perception of nurses’ uniform adequacy to the role and capability to reassure resulted improved (p < 0·0001, p = 0·0003).

Conclusions:  Multi‐coloured non‐conventional attire were preferred by hospitalised children and their parents. Their introduction improved the perception children have of their nurses. Moreover, the coloured uniforms improve the parents perception about the reliability of the nurse.

Relevance to clinical practice:  The use of non‐conventional nurses’ attire can contribute to improve the child–nurse relation, which has the potential to ease the discomfort experienced by children due to hospitalisation.
Restraint use among nursing home residents: cross‐sectional study and prospective cohort study
Authors: Meyer Gabriele , Köpke Sascha , Haastert Burkhard , Mühlhauser Ingrid
Published: October 2008

Aims and objectives.  To investigate (1) the prevalence of physical restraints and psychoactive medication, (2) newly administered physical restraints, frequency of application of the devices and frequency of psychoactive medication on demand during 12‐month follow‐up and (3) characteristics associated with restraint use in nursing homes.

Background.  High quality data on restraint use in German nursing homes are lacking so far. Such information is the basis for interventions to achieve a restraint‐free care.

Design.  Cross‐sectional study and prospective cohort study.

Setting and subjects.  Thirty nursing homes with 2367 residents in Hamburg, Germany.

Methods.  External investigators obtained prevalence of physical restraints by direct observation on three occasions on one day, psychoactive drugs were extracted from residents’ records and prospective data were documented by nurses.

Results.  Residents’ mean age was 86 years, 81% were female. Prevalence of residents with at least one physical restraint was 26·2% [95% confidence interval (CI) 21·3–31·1]. Centre prevalence ranged from 4·4 to 58·9%. Bedrails were most often used (in 24·5% of residents), fixed tables, belts and other restraints were rare. Prevalence of residents with at least one psychoactive drug was 52·4% (95% CI 48·7–56·1). The proportion of residents with at least one physical restraint after the first observation week of 26·3% (21·3–31·3) cumulated to 39·5% (33·3–45·7) at the end of follow‐up (10·4 SD 3·3 months). The relative frequency of observation days with at least one device ranged from 4·9–64·8% between centres. No characteristic was found to explain centre differences.

Conclusions.  The frequency of physical restraints and psychoactive drugs in German nursing homes is substantial. Pronounced centre variation suggests that standard care is possible without restraints.

Relevance to clinical practice.  Effective restraint minimisation approaches are urgently warranted. An evidence‐based guideline may overcome centre differences towards a restraint‐free nursing home care.
Metasynthesis: withdrawing life‐sustaining treatments: the experience of family decision‐makers
Authors: Meeker Mary Ann , Jezewski Mary Ann
Published: October 2008

Aim.  The present study was undertaken to synthesise findings from qualitative investigations of family participation in decisions to withdraw and/or withhold life‐sustaining treatment from a seriously ill family member.

Background.  As a consequence of increasing effectiveness and sophistication of available medical interventions, death is commonly preceded by a decision to withdraw or withhold potentially life‐sustaining treatments. These decisions take place in a bioethical context characterised by the preeminence of self‐determination, but patients are typically too ill to make their own decisions. Thus, family members are called upon to participate in these morally consequential decisions on the patient’s behalf.

Design.  Metasynthesis

Method.  Metasynthesis is a form of inquiry that provides for integration of qualitative studies’ findings to strengthen knowledge for practice and advance theoretical development. This metasynthesis was conducted using the constant comparative methods of grounded theory.

Results.  Family members engage in a process of participation in decision‐making that is comprised of three major categories: reframing reality, relating and integrating. Surrogates used both cues and information as they reframed their understanding of the patient’s status. Relationships with providers and with other family members powerfully influenced the decision‐making process. Integrating was characterised by reconciling and going forward. This part of the process has both intrapersonal and interpersonal aspects and describes how family decision‐makers find meaning in their experience and move forward in their lives.

Conclusions.  This synthesis provides a more comprehensive and empirically supported understanding of family members’ experiences as they participate in treatment decisions for dying family members.

Relevance to clinical practice.  This metasynthesis provides evidence to improve family care during treatment withdrawal/withholding decision‐making and a theoretical model that can be used to guide creation of clinical practice guidelines. Through increased understanding of family members’ experiences, clinicians can more effectively support family decision‐making processes.
Using the caring dimensions inventory as an indicator of person‐centred nursing
Authors: McCance Tanya , Slater Paul , McCormack Brendan
Published: October 2008

Aims.  This paper reports findings from a large‐scale quasi‐experimental study that used a measure of caring as a means of evaluating person‐centred nursing and aims to illustrate the synergy between the concepts of caring and person‐centredness.

Background.  Evidence would suggest that effective person‐centred nursing requires the formation of therapeutic relationships between professionals, patients and others significant to them in their lives and that these relationships are built on mutual trust, understanding and a sharing of collective knowledge. This correlates with the conceptualisation of caring that is underpinned by humanistic nursing theories.

Design.  A pretest post‐test design was used in this study to evaluate the effect of person‐centred nursing on a range of outcomes, one of which was nurses’ and patients’ perception of caring.

Methods.  The Person‐Centred Nursing Index was the main data collection tool. The Caring Dimension Inventory and Nursing Dimensions Inventory, were component parts of the Person‐Centred Nursing Index and were used to measure nurses’ and patients’ perceptions of caring. The Person‐Centred Nursing Index was administered at five points in time over a two‐year intervention period.

Results.  Nurses had a clear idea of what constituted caring in nursing, identifying statements that were reflective of person‐centredness, which was consistent over time. This was in contrast to patients, whose perceptions were more variable, highlighting incongruencies that have important implications for developing person‐centred practice.

Conclusion.  The findings confirm the Caring Dimension Inventory/Nursing Dimensions Inventory as an instrument that can be used as an indicator of person‐centred practice. Furthermore, the findings highlight the potential of such instruments to generate data on aspects of nursing practice that are traditionally hard to measure.

Relevance to clinical practice.  The findings would suggest that nurses need to be aware of patients’ perceptions of caring and use this to influence changes in practice, where the prime goal is to promote person‐centredness.