bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex steroid hormones in pairs of tumor and serum from breast cancer patients and pathobiological role of androstene‐3β, 17β‐diol
Authors: Honma Naoko , Saji Shigehira , Hirose Makiko , Horiguchi Shin‐ichiro , Kuroi Katsumasa , Hayashi Shin‐ichi , Utsumi Toshiaki , Harada Nobuhiro
Published: June 2011

Estrogens play an important role in the pathobiology of breast cancer. In postmenopausal women, peripheral synthesis of estrogens from adrenal/ovarian androgens, dehydroepiandrosterone (DHEA) or androstenedione (Adione), by estrogen‐metabolizing enzymes is important. Besides estrone (E1) and estradiol (E2), androgen metabolites, such as androstene‐3β, 17β‐diol (Aenediol) or 5α‐androstane‐3β, 17β‐diol (Aanediol), are known to have estrogenic functions, although they have been studied much less in breast cancer. To precisely elucidate steroid metabolism in breast cancer patients and to identify the pathobiological role of estrogenic androgen metabolites, concentrations of DHEA, Adione, Aenediol, Aanediol, E1, and E2 in pairs of serum and tumor tissue from patients with primary breast cancer were measured by liquid chromatography‐tandem mass spectrometry. Cell proliferation assays using Aenediol were performed for four breast cancer cell lines. Serous E2 concentration was extremely low in postmenopausal women; however, a marked increase in tumor tissue was observed in hormone receptor‐positive cases. E1 concentration, in contrast, was sustained at a higher level, even in postmenopausal serum, and did not increase in tumor tissue irrespective of the hormone receptor status. Dehydroepiandrosterone was most abundant in all samples, and exhibited a similar pattern as Adione and Aenediol. 5α‐Androstane‐3β, 17β‐diol was undetectable in most samples. Androstene‐3β, 17β‐diol proliferated estrogen receptor‐α‐positive breast cancer cells in the absence of E2. The intratumoral increase of E2, but not E1, in hormone receptor‐positive postmenopausal breast cancer tissue, as well as the proliferative role of Aenediol, was elucidated. (Cancer Sci 2011; 102: 1848–1854)
Overexpression of neurone glial‐related cell adhesion molecule is an independent predictor of poor prognosis in advanced colorectal cancer
Authors: Chan Jason Y. , Ong Chee W. , Salto‐Tellez Manuel
Published: June 2011

A downstream target of the Wnt pathway, neurone glial‐related cell adhesion molecule (Nr‐CAM) has recently been implicated in human cancer development. However, its role in colorectal cancer (CRC) pathobiology and clinical relevance remains unknown. In this study, we examined the clinical significance of Nr‐CAM protein expression in a retrospective series of 428 CRCs using immunohistochemistry and tissue microarrays. Cox proportional hazards regression was used to calculate hazard ratios (HR) of mortality according to various clinicopathological features and molecular markers. All CRC samples were immunoreactive for Nr‐CAM protein expression, compared to 10/245 (4%) matched normal tissue (P < 0.0001). Of 428 CRC samples, 97 (23%) showed Nr‐CAM overexpression, which was significantly associated with nodal (P = 0.012) and distant (P = 0.039) metastasis, but not with extent of local invasion or tumor size. Additionally, Nr‐CAM overexpression was associated with vascular invasion (P = 0.0029), p53 expression (P = 0.036), and peritoneal metastasis at diagnosis (P = 0.013). In a multivariate model adjusted for other clinicopathological predictors of survival, Nr‐CAM overexpression correlated with a significant increase in disease‐specific (HR 1.66; 95% confidence interval 1.11–2.47; P = 0.014) and overall mortality (HR 1.57; 95% confidence interval 1.07–2.30; P = 0.023) in advanced but not early stage disease. Notably, 5‐fluorouracil‐based chemotherapy conferred significant survival benefit to patients with tumors negative for Nr‐CAM overexpression but not to those with Nr‐CAM overexpressed tumors. In conclusion, Nr‐CAM protein expression is upregulated in CRC tissues. Nr‐CAM overexpression is an independent marker of poor prognosis among advanced CRC patients, and is a possible predictive marker for non‐beneficence to 5‐fluorouracil‐based chemotherapy. (Cancer Sci 2011; 102: 1855–1861)
Alcohol consumption, problem drinking, abstention and disability pension award. The Nord‐Trøndelag Health Study (HUNT)
Authors: Skogen Jens Christoffer , Knudsen Ann Kristin , Mykletun Arnstein , Nesvåg Sverre , Øverland Simon
Published: June 2011

Aims  To examine associations of abstention, alcohol consumption and problem drinking with subsequent disability pensioning (DP), and whether previous excessive consumption (‘sick‐quitting’) could explain some of the increased risk for DP among abstainers.

Design  Prospective population‐based study.

Setting and participants  Data were from two waves of the Nord‐Trøndelag Health Study (HUNT) linked with the national insurance database. The two main analyses included 37 729 (alcohol consumption) and 34 666 (problem drinking) participants.

Measurements  Alcohol consumption was measured by self‐reported consumption, while problem drinking was assessed by the Cut down, Annoyed, Guilt, Eye‐opener (CAGE) questionnaire. Information on subsequent DP, including diagnosis for which the DP was awarded, was gathered from the national insurance database. Covariates included somatic illness and symptoms, mental health, health‐related behaviour, socio‐economic status and social activity.

Findings  Those reporting the highest level of alcohol consumption were not at increased risk for DP [hazard ratio (HR) 1.12, 95% confidence interval (CI): 0.92–1.38], whereas problem drinking was a strong predictor (HR 2.79, 95% CI: 2.08–3.75) compared to their corresponding reference groups. Alcohol abstainers were also at increased risk for DP, but among them, the previous consumers (HR 1.95, 95% CI: 1.48–2.57) and previous excessive consumers (HR 1.67, 95% CI: 1.01–2.74) were at higher risk for DP than constant abstainers.

Conclusions  Problem drinking is linked to subsequent requirement for a disability pension but mere alcohol consumption is not. This is partly explained by ‘sick‐quitting’.
Sertraline delays relapse in recently abstinent cocaine‐dependent patients with depressive symptoms
Authors: Oliveto Alison , Poling James , Mancino Michael J. , Williams D. Keith , Thostenson Jeff , Pruzinsky Rhonda , Gonsai Kishorchandra , Sofuoglu Mehmet , Gonzalez Gerardo , Tripathi Shanti , Kosten Thomas R.
Published: June 2011

Aims  Whether the selective serotonin re‐uptake inhibitor sertraline at 200 mg/day delays relapse in recently abstinent cocaine‐dependent individuals.

Design  The study involved a 12‐week, double‐blind, placebo‐controlled clinical trial with 2‐week residential stay followed by 10‐week out‐patient participation.

Setting  Veterans Affairs residential unit and out‐patient treatment research program.

Participants  Cocaine‐dependent volunteers (n = 86) with depressive symptoms (Hamilton score > 15), but otherwise no major psychiatric or medical disorder or contraindication to sertraline.

Measurements  Participants were housed on a drug‐free residential unit (weeks 1–2) and randomized to receive sertraline or placebo. Participants then participated on an out‐patient basis during weeks 3–12 while continuing to receive study medication. Patients participated in a day substance abuse/day treatment program during weeks 1–3 and underwent weekly cognitive behavioral therapy during weeks 4–12. The primary outcome measure was thrice‐weekly urine results and the secondary measure was Hamilton Depression scores.

Findings  Pre‐hoc analyses were performed on those who participated beyond week 2. Generally, no group differences in retention or baseline characteristics occurred. Sertraline patients showed a trend towards longer time before their first cocaine‐positive urine (‘lapse’, χ2 = 3.67, P = 0.056), went significantly longer before having two consecutive urine samples positive for cocaine (‘relapse’, χ2 = 4.03, P = 0.04) and showed significantly more days to lapse (26.1 ± 16.7 versus 13.2 ± 10.5; Z = 2.89, P = 0.004) and relapse (21.3 ± 10.8 versus 32.3 ± 14.9; Z = 2.25, P = 0.02). Depression scores decreased over time (F = 43.43, P < 0.0001), but did not differ between groups (F = 0.09, P = 0.77).

Conclusions  Sertraline delays time to relapse relative to placebo in cocaine‐dependent patients who initially achieve at least 2 weeks of abstinence.
Benzodiazepines revisited—will we ever learn?
Authors: Lader Malcolm
Published: June 2011

Aims  To re‐examine various aspects of the benzodiazepines (BZDs), widely prescribed for 50 years, mainly to treat anxiety and insomnia. It is a descriptive review based on the Okey Lecture delivered at the Institute of Psychiatry, King's College London, in November 2010.

Methods  A search of the literature was carried out in the Medline, Embase and Cochrane Collaboration databases, using the codeword ‘benzodiazepine(s)’, alone and in conjunction with various terms such as ‘dependence’, ‘abuse’, etc. Further hand‐searches were made based on the reference lists of key papers. As 60 000 references were found, this review is not exhaustive. It concentrates on the adverse effects, dependence and abuse.

Results  Almost from their introduction the BZDs have been controversial, with polarized opinions, advocates pointing out their efficacy, tolerability and patient acceptability, opponents deprecating their adverse effects, dependence and abuse liability. More recently, the advent of alternative and usually safer medications has opened up the debate. The review noted a series of adverse effects that continued to cause concern, such as cognitive and psychomotor impairment. In addition, dependence and abuse remain as serious problems. Despite warnings and guidelines, usage of these drugs remains at a high level. The limitations in their use both as choice of therapy and with respect to conservative dosage and duration of use are highlighted. The distinction between low‐dose ‘iatrogenic’ dependence and high‐dose abuse/misuse is emphasized.

Conclusions  The practical problems with the benzodiazepines have persisted for 50 years, but have been ignored by many practitioners and almost all official bodies. The risk–benefit ratio of the benzodiazepines remains positive in most patients in the short term (2–4 weeks) but is unestablished beyond that time, due mainly to the difficulty in preventing short‐term use from extending indefinitely with the risk of dependence. Other research issues include the possibility of long‐term brain changes and evaluating the role of the benzodiazepine antagonist, flumazenil, in aiding withdrawal.
Evaluation of systolic murmurs using transthoracic echocardiography by anaesthetic trainees
Authors: Cowie B. , Kluger R.
Published: June 2011

Focused transthoracic echocardiography by anaesthetists in the peri‐operative period has recently been described; the data suggest that the specific skills required can be obtained by non cardiology physicians with limited training. Aortic stenosis is known to increase significantly the peri‐operative risk in non‐cardiac surgery. This study aimed to assess the ability of echocardiography naive trainee anaesthetists to recognise and assess the severity of aortic stenosis after a set amount of training. Five trainees underwent 2 h of didactic and hands‐on teaching in evaluation of the aortic valve, after which they scanned 20 patients each. Their results were compared with those obtained by an experienced cardiac anaesthetist with echocardiography training and qualifications. There was 100% concordance between trainees and the consultant for assessment of clinically significant aortic stenosis, with no cases of misdiagnosis. There was also 90–100% agreement (kappa statistic 0.8–1) between the consultant and each trainee’s assessment of clinically significant aortic stenosis based on a peak aortic velocity > 3 m.sec−1. Anaesthesia trainees can be successfully and rapidly trained to recognise and estimate the severity of aortic stenosis.
Ultraviolet B radiation and reactive oxygen species modulate interleukin-31 expression in T lymphocytes, monocytes and dendritic cells
Authors: Cornelissen C. , Brans R. , Czaja K. , Skazik C. , Marquardt Y. , Zwadlo-Klarwasser G. , Kim A. , Bickers D.R. , Lüscher-Firzlaff J. , Lüscher B. , Baron J.M.
Published: June 2011

Background Interleukin (IL)-31 is a novel Th2 T-cell cytokine that induces pruritus and dermatitis in transgenic mice. While enhanced mRNA expression of this cytokine is detected in skin samples of inflammatory skin diseases, the regulation of IL-31 expression is poorly understood.

Objectives To assess the effects of ultraviolet (UV) B radiation and H2O2 on IL-31 mRNA and protein expression in skin and different peripheral blood mononuclear cells (PBMCs).

Methods The effects of UVB radiation and H2O2, as a prototypic reactive oxygen species, on IL-31 mRNA and protein expression were analysed in various inflammation-related cells and murine skin tissue.

Results Treatment of cells with UVB radiation and H2O2 strongly induced IL-31 mRNA and protein expression in human PBMCs and in the skin of SKH-1 mice. Following exposure to UVB or H2O2, we observed increased expression of IL-31 mRNA in T cells, monocytes, macrophages, and immature and especially mature dendritic cells. H2O2 treatment but not UVB radiation led to a moderate upregulation of IL-31 mRNA expression in epidermal keratinocytes and dermal fibroblasts. Pretreatment of T lymphocytes with the MAPK p38 inhibitor SB203580 or the MEK1 inhibitor U0126 reduced the stimulatory effect of H2O2. These experiments suggest that p38 is involved in the regulation of IL-31 expression in human skin.

Conclusions Our studies reveal that UVB and reactive oxygen species stimulate the expression of IL-31 in PBMCs and skin, especially in T cells, monocytes and monocyte-derived dendritic cells.
Merkel cell carcinoma in Western Australia: a population-based study of incidence and survival
Authors: Girschik J. , Thorn K. , Beer T.W. , Heenan P.J. , Fritschi L.
Published: June 2011

Background Merkel cell carcinoma (MCC) is an uncommon but aggressive cutaneous skin cancer. Even with the appropriate treatment, MCC is prone to recurrence, and metastases are common. Exposure to ultraviolet radiation has been suggested as contributing towards the development of MCC. MCC has not been extensively investigated in Australia, even though Australia has the highest incidence of sun-related cancers in the world.

Objectives To describe the demographics and determine trends of incidence and survival of MCC cases in Western Australia (WA).

Methods All reported invasive cases of MCC incident between 1 January 1993 and 31 December 2007 were extracted from the WA Cancer Registry. Age-adjusted incidence rates for MCC were calculated using direct standardization to the U.S. standard 2000 population. Cause-specific survival was investigated using Kaplan–Meier and Cox proportional hazards analysis.

Results Two hundred and fifteen cases were confirmed by pathological review as being definite cases of MCC. Patients were mainly males (65%) and elderly (median age 77 years). Standardized age-adjusted incidence rates were higher in men (1·0/100 000) than in women (0·63/100 000) and higher in older ages (15·5/100 000 in the 85+ year age group) than younger ages (0·1/100 000 in the 30–34 year age group). Five-year cause-specific survival was 64%.

Conclusions Incidence of MCC in WA is the highest reported in the literature. In addition, MCC has worse survival than melanoma. The high rates and demographic and anatomical distribution are consistent with sun exposure playing a causal role.
Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis
Authors: Fukushi S. , Yamasaki K. , Aiba S.
Published: June 2011

Background Prurigo nodularis (PN) is a chronic dermatitis characterized by discrete, raised, and firm papulonodules with intense pruritus. The pathogenesis still remains to be elucidated.

Objectives To clarify the role of Th1 and Th2 cytokines in the pathogenesis of PN.

Methods We examined the cytokine signatures, such as phosphorylation of STAT1, STAT3 and STAT6, HLA-DR and hyaluronan accumulation, to reveal the Th1 and Th2 cytokine influence on the lesional epidermis of PN.

Results We first optimized antigen retrieval methods to detect these signatures with antibodies for phospho-STAT1 (pSTAT1), phospho-STAT3 (pSTAT3), phospho-STAT6 (pSTAT6), HLA-DR and hyaluronic acid binding protein (HABP) on the formalin-fixed paraffin-embedded sections of psoriasis, lichen planus and atopic dermatitis biopsy samples. Activation of STAT1 and STAT6 in epidermis by Th1 and Th2 cytokines was further confirmed in a cultured skin equivalent model treated with interferon-γ or interleukin (IL)-4/IL-13. With the relevant immunostaining methods, we examined the cytokine signatures in 22 cases of PN. The results revealed that (i) the entire epidermis of 19 cases was stained with anti-pSTAT6 antibody, (ii) 21 cases demonstrated nuclear staining with anti-pSTAT3 antibody, (iii) the entire epidermis of 21 cases was stained with HABP, (iv) the epidermis of eight cases showed scattered staining with anti-pSTAT1 antibody, and (v) six cases were positive for HLA-DR membrane expression.

Conclusions These data indicated that Th2 cytokines related to STAT6 activation together with some unknown stimuli that activate STAT3 play a principal role in the pathogenesis of PN.
Lenalidomide downregulates the cell survival factor, interferon regulatory factor‐4, providing a potential mechanistic link for predicting response
Authors: Lopez‐Girona Antonia , Heintel Daniel , Zhang Ling‐Hua , Mendy Derek , Gaidarova Svetlana , Brady Helen , Bartlett Justin Blake , Schafer Peter H. , Schreder Martin , Bolomsky Arnold , Hilgarth Bernadette , Zojer Niklas , Gisslinger Heinz , Ludwig Heinz , Daniel Tom , Jäger Ulrich , Chopra Rajesh
Published: June 2011

Overexpression of the transcription factor interferon regulatory factor‐4 (IRF4), which is common in multiple myeloma (MM), is associated with poor prognosis. Patients with higher IRF4 expression have significantly poorer overall survival than those with low IRF4 expression. Lenalidomide is an IMiD® immunomodulatory compound that has both tumouricidal and immunomodulatory activity in MM. This study showed that lenalidomide downregulated IRF4 levels in MM cell lines and bone marrow samples within 8 h of drug exposure. This was associated with a decrease in MYC levels, as well as an initial G1 cell cycle arrest, decreased cell proliferation, and cell death by day 5 of treatment. In eight MM cell lines, high IRF4 levels correlated with increased lenalidomide sensitivity. The clinical significance of this observation was investigated in 154 patients with MM. Among MM patients with high levels of IRF4 expression, treatment with lenalidomide led to a significantly longer overall survival than other therapies in a retrospective analysis. These data confirm the central role of IRF4 in MM pathogenesis; indicate that this is an important mechanism by which lenalidomide exerts its antitumour effects; and may provide a mechanistic biomarker to predict response to lenalidomide.
Epigenetic silencing of MIR203 in multiple myeloma
Authors: Wong Kwan‐Yeung , Liang Raymond , So Chi‐Chiu , Jin Dong‐Yan , Costello Joseph F. , Chim Chor‐Sang
Published: June 2011

Epigenetic inactivation of tumour suppressor microRNAs has been implicated in carcinogenesis. We studied the promoter methylation of MIR203 in eight normal marrow controls, eight multiple myeloma (MM) cell lines, 20 monoclonal gammopathy of undetermined significance (MGUS), 123 diagnostic MM and 19 relapsed MM samples by methylation‐specific polymerase chain reaction. Promoter of MIR203 was unmethylated in normal controls but homozygously methylated in 25% MM cell lines. Treatment with 5‐Aza‐2′‐deoxycytidine led to promoter demethylation and MIR203 re‐expression. Cyclic AMP responsive element binding protein 1 (CREB1) mRNA was predicted as a MIR203 direct target. Luciferase activity was reduced in constructs carrying wild‐type CREB1 3′UTR upon MIR203 expression but not in those carrying mutant CREB1 3′UTR. Moreover, restoration of MIR203 led to downregulation of CREB1 protein and inhibition of myeloma cell proliferation. In primary samples, MIR203 methylation occurred in 25·0% MGUS, 23·6% diagnostic MM, and 21·1% relapsed MM samples. In conclusion, MIR203 methylation is disease‐specific with reversible gene silencing in MM. MIR203 is a tumour suppressor microRNA inhibiting cellular proliferation by targeting CREB1 mRNA in MM. Comparable occurrence of MIR203 methylation in MGUS and MM at diagnosis or relapse suggested that MIR203 methylation may be an early event in myelomagenesis instead of being acquired during disease progression.
Intermediate dose of imatinib in combination with chemotherapy followed by allogeneic stem cell transplantation improves early outcome in paediatric Philadelphia chromosome‐positive acute lymphoblastic leukaemia (ALL): results of the Spanish Cooperative Group SHOP studies ALL‐94, ALL‐99 and ALL‐2005
Authors: Rives Susana , Estella Jesús , Gómez Pedro , López‐Duarte Mónica , de Miguel Purificación García , Verdeguer Amparo , Moreno Maria José , Vivanco José Luis , Couselo José Miguel , Fernández‐Delgado Rafael , Maldonado Marisol , Tasso María , López‐Ibor Blanca , Lendínez Francisco , López‐Almaraz Ricardo , Uriz Javier , Melo Montserrat , Fernández‐Teijeiro Ana , Rodríguez Isidoro , Badell Isabel
Published: June 2011

Philadelphia‐chromosome acute lymphoblastic leukaemia (Ph+ ALL) is a subgroup of ALL with very high risk of treatment failure. We report here the results of the Sociedad Española de Hematología y Oncología Pediátricas (SEHOP/SHOP) in paediatric Ph+ ALL treated with intermediate‐dose imatinib concurrent with intensive chemotherapy. The toxicities and outcome of these patients were compared with historical controls not receiving imatinib. Patients with Ph+ ALL aged 1–18 years were enrolled in three consecutive ALL/SHOP trials (SHOP‐94/SHOP‐99/SHOP‐2005). In the SHOP‐2005 trial, imatinib (260 mg/m2 per day) was given on day‐15 of induction. Allogeneic haematopoietic stem‐cell transplantation (HSCT) from a matched related or unrelated donor was scheduled in first complete remission (CR1). Forty‐three patients were evaluable (22 boys, median age 6·8 years, range, 1·2–15). Sixteen received imatinib whereas 27 received similar chemotherapy without imatinib. Seventeen of 27 and 15 of 16 patients in the non‐imatinib and imatinib cohort, respectively, underwent HSCT in CR1. With a median follow‐up of 109 and 39 months for the non‐imatinib and imatinib cohorts, the 3‐year event‐free survival (EFS) was 29·6% and 78·7%, respectively (P = 0·01). These results show that, compared to historical controls, intermediate dose of imatinib given concomitantly with chemotherapy and followed by allogeneic HSCT markedly improved early EFS in paediatric Ph+ ALL.
Reduced‐intensity conditioning haematopoietic cell transplantation for haemophagocytic lymphohistiocytosis: an important step forward
Authors: Marsh Rebecca A. , Jordan Michael B. , Filipovich Alexandra H.
Published: June 2011

Haemophagocytic lymphohistiocytosis (HLH) is a life‐threatening immunodeficiency characterized by severe systemic hyper‐inflammatory responses to infectious or other triggers of the immune system. In many patients, the underlying cause of HLH is a genetic defect leading to defective CD8+ T cell and natural killer cell granule‐mediated cytotoxicity. The treatment of HLH consists principally of immune suppression followed by allogeneic haematopoietic cell transplantation (HCT) to cure the underlying defect and prevent relapse of HLH. Initial treatment regimens consist of steroids coupled with either etoposide or antithymocyte globulin, ± ciclosporin. Complete responses are observed in only 50–75% of patients and even after a complete response, relapse and death still occur. The only definitive, long‐term cure for patients with genetic forms of HLH is allogeneic HCT. Unfortunately, allogeneic HCT for patients with HLH is often complicated by critical illness, extensive organ involvement, active infections, or refractory HLH. For these reasons, patients are unusually prone to developing transplant‐related toxicities and complications. In recent years, great strides have been made with regard to the care and transplantation of patients with HLH. Here we review the current state of the treatment of patients with HLH with allogeneic HCT, highlighting the important steps forward that have been made with reduced‐intensity conditioning.
Biweekly rituximab, cyclophosphamide, vincristine, non‐pegylated liposome‐encapsulated doxorubicin and prednisone (R‐COMP‐14) in elderly patients with poor‐risk diffuse large B‐cell lymphoma and moderate to high ‘life threat’ impact cardiopathy
Authors: Corazzelli Gaetano , Frigeri Ferdinando , Arcamone Manuela , Lucania Anna , RosariaVilla Maria , Morelli Emanuela , Amore Alfonso , Capobianco Gaetana , Caronna Antonietta , Becchimanzi Cristina , Volzone Francesco , Marcacci Gianpaolo , Russo Filippo , De Filippi Rosaria , Mastrullo Lucia , Pinto Antonio
Published: June 2011

This Phase II study assessed feasibility and efficacy of a biweekly R‐COMP‐14 regimen (rituximab, cyclophosphamide, non‐pegylated liposome‐encapsulated doxorubicin, vincristine and prednisone) in untreated elderly patients with poor‐risk diffuse large B‐cell lymphoma (DLBCL) and moderate to high ‘life threat’ impact NIA/NCI cardiac comorbidity. A total of 208 courses were delivered, with close cardiac monitoring, to 41 patients (median age: 73 years, range: 62–82; 37% >75 years) at a median interval of 15·6 (range, 13–29) days; 67% completed all six scheduled courses. Response rate was 73%, with 68% complete responses (CR); 4‐year disease‐free survival (DFS) and time to treatment failure (TTF) were 72% and 49%, respectively. Failures were due to early death (n = 3), therapy discontinuations (no‐response n = 2; toxicity n = 6), relapse (n = 6) and death in CR (n = 3). Incidence of cardiac grade 3–5 adverse events was 7/41 (17%; 95% confidence interval: 8–31%). Time to progression and overall survival at 4‐years were 77% and 67%, respectively. The Age‐adjusted Charlson Comorbidity Index (aaCCI) correlated with failures (P = 0·007) with patients scoring ≤7 having a longer TTF (66% vs. 29%; P = 0·009). R‐COMP‐14 is feasible and ensures a substantial DFS to poor‐risk DLBCL patients who would have been denied anthracycline‐based treatment due to cardiac morbidity. The aaCCI predicted both treatment discontinuation rate and TTF.
Protective pathways against colitis mediated by appendicitis and appendectomy
Authors: Cheluvappa R , Luo A S , Palmer C , Grimm M C
Published: June 2011

Appendicitis followed by appendectomy (AA) at a young age protects against inflammatory bowel disease (IBD). Using a novel murine appendicitis model, we showed that AA protected against subsequent experimental colitis. To delineate genes/pathways involved in this protection, AA was performed and samples harvested from the most distal colon. RNA was extracted from four individual colonic samples per group (AA group and double-laparotomy control group) and each sample microarray analysed followed by gene-set enrichment analysis (GSEA). The gene-expression study was validated by quantitative reverse transcription–polymerase chain reaction (RT–PCR) of 14 selected genes across the immunological spectrum. Distal colonic expression of 266 gene-sets was up-regulated significantly in AA group samples (false discovery rates < 1%; P-value < 0·001). Time–course RT–PCR experiments involving the 14 genes displayed down-regulation over 28 days. The IBD-associated genes tnfsf10, SLC22A5, C3, ccr5, irgm, ptger4 and ccl20 were modulated in AA mice 3 days after surgery. Many key immunological and cellular function-associated gene-sets involved in the protective effect of AA in experimental colitis were identified. The down-regulation of 14 selected genes over 28 days after surgery indicates activation, repression or de-repression of these genes leading to downstream AA-conferred anti-colitis protection. Further analysis of these genes, profiles and biological pathways may assist in developing better therapeutic strategies in the management of intractable IBD.
A concerted decline in insulin secretion and action occurs across the spectrum of fasting and postchallenge glucose concentrations
Authors: Sathananthan Airani , Man Chiara Dalla , Zinsmeister Alan R. , Camilleri Michael , Rodeheffer Richard J. , Toffolo Gianna , Cobelli Claudio , Rizza Robert A. , Vella Adrian
Published: June 2011

Aims/hypothesis  Individuals with impaired fasting glucose (IFG) are at increased risk of developing diabetes over the subsequent decade. However, there is uncertainty as to the mechanisms contributing to the development of diabetes. We sought to quantitate insulin secretion and action across the prediabetic range of fasting glucose.

Methods  We studied a cohort of 173 individuals with a fasting glucose concentration <7·0 mm after an overnight fast using a 75‐g oral glucose tolerance test (OGTT). Insulin action (Si) was estimated using the oral glucose minimal model, and β‐cell responsivity indices (φ) were estimated using the oral C‐peptide minimal model. The disposition index (DI) for each individual was calculated. The relationship of DI, φ and Si with fasting and postchallenge glucose, as well as other covariates, was explored using a generalized linear regression model.

Results  In this cross‐sectional study, Si and DI were inversely related to fasting glucose concentrations. On the other hand, φ was unrelated to fasting glucose concentrations. Si, φ and DI were all inversely related to area above basal glucose concentrations after glucose challenge. Multiple parameters including body composition and gender contributed to the variability of Si and DI at a given fasting or postchallenge glucose concentration.

Conclusions/interpretation  Defects in insulin secretion and action interact with body composition and gender to influence postchallenge glucose concentrations. There is considerable heterogeneity of insulin secretion and action for a given fasting glucose likely because of patient subsets with isolated IFG and normal glucose tolerance.
Liver stiffness and 30‐day mortality in a cohort of patients admitted to hospital
Authors: Lindvig Kristoffer , Mössner Belinda K. , Pedersen Court , Lillevang Søren T. , Christensen Peer.B.
Published: June 2011

Eur J Clin Invest 2011

Background  Transient elastography (TE) is a new noninvasive method to assess the degree of liver fibrosis by measuring liver stiffness. The objective of this study was to determine whether increased liver stiffness in patients admitted to medical wards was associated with increased 30‐day mortality.

Materials and methods  A prospective cohort study at the medical admissions ward at Odense University Hospital, Denmark, covering a population of 300 000 inhabitants. Consecutive patients ≥ 18 years of age were examined by TE (Fibroscan) at admission. Outcome measure was 30‐day mortality.

Results  Among 568 patients admitted during 24 days, 289 (50·8%) were included in the study, 212 (73·4%) with valid TE measurement. Increased liver stiffness (TE value > 8 kPa) was found in 22·6% (48/212). This was independently associated with cirrhosis of the liver (P < 0·001) and congestive heart failure (CHF) (P < 0·001). The estimated prevalence of cirrhosis was 7% (95% CI 4–11%). The 30‐day mortality among patients with TE value > 8 kPa was 20·8% (10/48, 95%CI 10·5–35·0%) compared to patients with TE value ≤ 8 kPa 3·7% (6/164, 95%CI 1·3–7·8%) (P < 0·001), and TE value > 8 kPa was an independent predictor of death.

Conclusions  Elevated TE value at admission is associated with increased mortality, cirrhosis of the liver and CHF. This information may potentially be used to improve the outcome of high‐risk patients admitted to hospital.
Trade‐off between travel distance and prioritization of high‐reward sites in traplining bumblebees
Authors: Lihoreau Mathieu , Chittka Lars , Raine Nigel E.
Published: June 2011

1. Animals exploiting renewable resource patches are faced with complex multi‐location routing problems. In many species, individuals visit foraging patches in predictable sequences called traplines. However, whether and how they optimize their routes remains poorly understood.

2. In this study, we demonstrate that traplining bumblebees (Bombus terrestris) make a trade‐off between minimizing travel distance and prioritizing the most rewarding feeding locations.

3. Individual bees trained to forage on five artificial flowers of equal reward value selected the shortest possible route as a trapline. After introducing a single highly rewarding flower to the array, they re‐adjusted their routes visiting the most rewarding flower first provided the departure distance from the shortest possible route remained small (18%). When routes optimizing the initial rate of reward intake were much longer (42%), bees prioritized short travel distances.

4. Under natural conditions, in which individual flowers vary in nectar productivity and replenish continuously, it might pay bees to prioritize highly rewarding locations, both to minimize the overall number of flowers to visit and to beat competitors.

5. We discuss how combined memories of location and quality of resource patches could allow bees and other traplining animals to optimize their routing decisions in heterogeneous environments.
Tree architecture and life‐history strategies across 200 co‐occurring tropical tree species
Authors: Iida Yoshiko , Kohyama Takashi S. , Kubo Takuya , Kassim Abd Rahman , Poorter Lourens , Sterck Frank , Potts Matthew D.
Published: June 2011

1. Tree architecture is thought to allow species to partition horizontal and vertical light gradients in the forest canopy. Tree architecture is closely related to light capture, carbon gain and the efficiency with which trees reach the canopy. Previous studies that investigated how light gradients drive differentiation in tree architecture have produced inconsistent results, partially because of the differences in which tree species and ontogenetic stages were studied.

2. We examined the relationship between stem diameter, tree height, foliage height, crown width and life‐history strategy over a broad size range of 200 randomly selected, co‐occurring tree species in a lowland rainforest in Peninsular Malaysia. We developed a hierarchical Bayesian model to account for both intra‐ and interspecific variation and describe the relationships among tree architectural variables. We analysed interspecific variation in tree architectural variables in relation to adult stature and light requirement for species regeneration as a function of tree size.

3. There was little interspecific variation in architectural variables, this is partly because of large intraspecific variation in response to canopy heterogeneity, but it also suggests architectural convergence within this community. However, interspecific analyses showed that, for large‐statured species, small size classes had thinner stems with narrow and shallow crowns, whereas large‐size classes had wider crowns. Light‐demanding species (as indicated by high sapling mortality in shaded conditions) showed weak trends in tree architecture and were only characterized by wide crowns at intermediate sizes.

4. In summary, tree architectural traits overlapped across the species community. This suggests that architectural convergence and equalizing effects occur in this diverse tropical forest and that community‐wide allometric equations can be used to describe forest height and carbon storage. Light resource partitioning also occurs, indicating stabilizing effects. Interspecific architectural variation in relation to adult stature supports the theory of the trade‐off between early reproduction and vegetative growth. In closed rainforests, adult stature imposes a stronger force on architectural differentiation of species than regeneration light requirements.
Approach to the treatment, characterization and diagnosis of an acquired auto‐antibody directed against factors prothrombin, factor X and factor IX: a case report and review of the literature
Authors: ROCHANDA L. , Del ZOPPO G. J. , FEINSTEIN D. I. , LIEBMAN H. A.
Published: June 2011

Summary.  Bleeding disorders secondary to acquired non‐inhibitory antibodies directed against vitamin K‐dependent coagulation proteins are rare. In this report, the authors describe a patient with a low grade lymphoma who presented with a fatal acquired bleeding manifestation and abnormal hemostatic studies resulting from deficiencies in both prothrombin and factor X. Patient plasma samples were collected and studied for the presence of an acquired inhibitor. Levels of plasma coagulation proteins were measured using immunoassay. Patient anti‐prothrombin immunoglobulin G was isolated and binding to prothrombin, prothrombin F1.2, factors IX and X was evaluated using immunoblots and competition immunoassay. Prolongation in the prothrombin time and activated partial thromboplastin time suggested a factor deficiency in the common pathway of coagulation. Functional and antigenic levels of both prothrombin and factor X were decreased. An IgG subtype‐4 antibody was isolated from patient plasma using affinity chromatography on prothrombin‐sepharose. This antibody was found to bind to a common metal‐ion‐dependent conformational epitope found on the γ‐carboxyglutamic acid (Gla) domain of prothrombin, factor X and factor IX. This report represents the first description of an acquired bleeding disorder resulting from a unique cross‐reactive auto‐antibody against a common metal‐ion‐dependent antigenic structure on the Gla‐domain of the vitamin K‐dependent proteins.
Compatibilisation of starch/poly(butylene adipate co‐terephthalate) blends in blown films
Authors: Olivato Juliana B. , Grossmann Maria V. E. , Yamashita Fabio , Nobrega Marcelo M. , Scapin Monica R. S. , Eiras Daniel , Pessan Luiz A.
Published: June 2011

Reactive extrusion was utilised for starch/poly(butylene adipate co‐terephthalate) (PBAT) blown film production, using maleic anhydride (MA) and citric acid (CA), alone or combined, as compatibilisers. These compounds (2% w/w) were added to the starch/PBAT (55:45) mixture after dispersion on glycerol. More rigid films, with greater tensile strength (9.82 ± 0.45 MPa), were produced when 2.0% CA was used. The opposite, little homogeneity and poor tensile strength (0.77 ± 0.12 MPa) and elongation (2.67 ± 0.67%) were found in films produced using 2.0% MA. Barrier properties to water vapour were improved by compatibilisers. FTIR analysis showed that CA and MA were able to promote esterification/transesterification reactions. Blends containing CA also showed better phase compatibilisation in the scanning electron microscopic images. It was found that in mixtures containing MA, the process and the concentration of this reagent need to be adapted to produce films with improved properties.
Psychometric testing of the Spanish version of the Practice Environment Scale of the Nursing Work Index in a primary healthcare context
Authors: De Pedro‐Gómez Joan , Morales‐Asencio José Miguel , Sesé‐Abad Albert , Bennasar‐Veny Miquel , Pericas‐Beltran Jordi , Miguélez‐Chamorro Angélica
Published: June 2011

de pedro‐gómez j., morales‐asencio j.m., sesé‐abad a., bennasar‐veny m., pericas‐beltran J. & miguélez‐chamorro a. (2012) Psychometric testing of the Spanish version of the Practice Environment Scale of the Nursing Work Index in a primary healthcare context. Journal of Advanced Nursing68(1), 212–221.

Aim.  This paper is a report of psychometric testing of the Spanish version of the Practice Environment Scale of the Nursing Work Index for use in a primary health care.

Background.  The Practice Environment Scale of the Nursing Work Index has been widely used in different studies and contexts. However, there is no validated version for primary care nursing staff in Spain.

Methods.  A descriptive, multicentre, cross‐sectional study for transcultural adaptation and psychometric validation purposes. Data were collected from October 2009 to January 2010. To test the reliability of the factors in the measurement model, Cronbach’s alpha was used. To study the measurement model, different structural models were tested, using exploratory and confirmatory factor analyses. 377 completed questionnaires were obtained from a total of 553 nurses working for the Public Health Service in the Balearic Islands (Spain). This represents a response rate of 68·2%.

Results.  For overall reliability, a Cronbach alpha of 0·91 was obtained. The confirmatory analysis upholds the original five‐factor structure.

Conclusion.  The excellent goodness of fit of the confirmatory analysis corroborates the validity of this adapted version in primary healthcare contexts.
Moderators of access and utilization of clinical preventive services in older adults
Authors: Garmon Bibb Sandra C. , Padden Diane L. , Ferguson Wakettia
Published: June 2011

garmon bibb s.c., padden d.l. & ferguson w. (2012) Moderators of access and utilization of clinical preventive services in older adults. Journal of Advanced Nursing 68(2), 335–348.

Aim.  This paper reports a study exploring the relationships between potential moderators of access and utilization of clinical preventive services in a homogeneous sample of older adults with near universal health coverage.

Background.  Advancements have occurred in eliminating financial and structural barriers to utilization of clinical preventive services (primary, secondary and tertiary prevention) in most developed countries, but variations in utilization continue. These variations may be attributed to non‐social determinants of health moderators that impact utilization in older adults.

Methods.  Theorized relationships were explored using questions from the United States Behavioral Risk Factor Surveillance System Survey and a homogenous convenience sample of 202 older adults (mean age 84; sd 5·23) with near universal health coverage. Data collected across a 2 year period (2007–2009) were analysed using Chi‐square, Mann–Whitney U and Hierarchical Logistic Regression.

Findings.  Several logistic regression models of personal access (advised to lose weight, high blood pressure, high cholesterol); moderators (gender, perceived health status, BMI ≥ 30 kg/m2); and clinical preventive services utilization (check‐up in last 12 months; ever had colonoscopy/sigmoidoscopy) showed statistically significant (P < 0·05) improvement in model fit by adding interaction terms (access X moderator).

Conclusion.  Exploring the impact of moderators on utilization may yield more insight into variations than could be explained by measurement of the direct affect of having near universal health coverage alone.
Usefulness of Aggressive Behaviour Risk Assessment Tool for prospectively identifying violent patients in medical and surgical units
Authors: Kim Son Chae , Ideker Kristyn , Todicheeney‐Mannes Dale
Published: June 2011

kim s.c., ideker k. & todicheeney‐mannes d. (2012) Usefulness of Aggressive Behaviour Risk Assessment Tool for prospectively identifying violent patients in medical and surgical units. Journal of Advanced Nursing 68(2), 349–357.

Aim.  The aim of this study is to evaluate the usefulness of the Aggressive Behaviour Risk Assessment Tool for prospectively identifying violent patients in medical‐surgical units.

Background.  Although patient violence against nurses is a serious occupational hazard, there is a lack of simple screening tools with acceptable sensitivity and specificity for identifying potentially violent patients in medical‐surgical units.

Methods.  A prospective cohort study involving patients admitted to six medical‐surgical units at an acute care hospital was conducted from August 2009 to December 2009. Primary nurses completed the 17‐item checklist within 24 hours of admission. A second identical checklist was completed by another nurse to assess the inter‐rater reliability. Following a violent event or just prior to discharge, the violent event outcome section was completed to collect information about violent event, if any. A multivariate logistic regression model with backward elimination was used to select a set of parsimonious items that best predict violent behaviours.

Results.  Fifty‐six patients out of 2063 (2·7%) had one or more violent events. A parsimonious set of ten items were selected for the tool. Receiver Operating Characteristics analysis of Aggressive Behaviour Risk Assessment Tool showed that the area under the curve was 0·82 (95% Confidence Interval, 0·75–0·90). The sensitivity and specificity at the cut‐off score of 1 were 70·9% and 89·3%, respectively. The Cohen’s Kappa for inter‐rater reliability was 0·647.

Conclusion.  The Aggressive Risk Assessment Tool is a simple, easy‐to‐use assessment tool with acceptable inter‐rater reliability, sensitivity and specificity that may be useful for prospectively identifying violent patients in medical‐surgical units.
Transcultural spirituality: the spiritual journey of hospitalized patients with schizophrenia in Taiwan
Authors: Yang Chun‐Tien , Narayanasamy Aru , Chang Sung‐Ling
Published: June 2011

Yang
C.‐T., Narayanasamy A. & Chang S.‐L. (2012) Transcultural spirituality: the spiritual journey of hospitalized patients with schizophrenia in Taiwan. Journal of Advanced Nursing 68(2), 358–367.

Aim.  The aim of this study was to explore how hospitalization and the diagnosis of schizophrenia have an impact on Taiwanese patients’ spiritual life.

Background.  Psychiatric nurses tend to construe patients’ spiritual issues as pathological problems and consequently are reluctant to address patient’s spirituality, which results in spirituality being overlooked in mental illness. An individual’s spiritual journey is dependent upon their cultural background and beliefs; however, the professional’s preconceived ideas suppress the voice of patients with schizophrenia to share their experiences of their spiritual journey. The lack of research exploring spirituality in mental illness in Taiwan means that spiritual care is overlooked in practice. This study sets out to explore spirituality from the perspectives of patients in two mental hospitals in Taiwan.

Methods.  Using a qualitative approach, 22 long‐term hospitalized patients diagnosed with schizophrenia were interviewed. Several themes from the data were identified using Ritchie and Spencer’s (1994) five stages analytical framework. The study was carried out from 2006 to 2008.

Results.  Patients revealed spiritual distress as a consequence of prolonged hospitalization. They used referents consistent with traditional Chinese philosophical perspectives derived from Taoism and Confucianism to describe various features of their spiritual distress and their longing for spiritual revival, transcendence and to be accepted as normal persons.

Conclusions.  In this age of globalization, nurses need to be fully cognisant of the cultural aspects of patients to respond to a mental health patient’s spirituality. Clinical and educational guidelines and policies could be developed for spiritual care in Taiwan.