bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA
Authors: Hendry Gordon J , Turner Deborah E , McColl John , Lorgelly Paula K , Sturrock Roger D , Watt Gordon F , Browne Michael , Gardner‐Medwin Janet , Friel Lorraine , Woodburn Jim 
Published: June 2009

AbstractBackgroundFoot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non‐medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non‐randomised clinical studies of single interventions that appear to under‐represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists.Methods/designAn exploratory phase II non‐pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio‐temporal and plantar‐pressure gait parameters, health related quality of life and semi‐quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow‐up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted.A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken.Trial RegistrationTrial registration number: UKCRN5045
Management of the critically poisoned patient
Authors: Boyle Jennifer S , Bechtel Laura K , Holstege Christopher P 
Published: June 2009

Abstract

Background
Clinicians are often challenged to manage critically ill poison patients. The clinical effects encountered in poisoned patients are dependent on numerous variables, such as the dose, the length of exposure time, and the pre-existing health of the patient. The goal of this article is to introduce the basic concepts for evaluation of poisoned patients and review the appropriate management of such patients based on the currently available literature.

Methods
An unsystematic review of the medical literature was performed and articles pertaining to human poisoning were obtained. The literature selected was based on the preference and clinical expertise of authors.

Discussion
If a poisoning is recognized early and appropriate testing and supportive care is initiated rapidly, the majority of patient outcomes will be good. Judicious use of antidotes should be practiced and clinicians should clearly understand the indications and contraindications of antidotes prior to administration.
Transplantation of selected or transgenic blood stem cells – a future treatment for HIV/AIDS?
Authors: Hütter Gero , Schneider Thomas , Thiel Eckhard 
Published: June 2009

Interaction with the chemokine receptor, CCR5, is a necessary precondition for maintaining HIV‐1 infection. Individuals with the CCR5‐delta32 deletion who lack this receptor are highly resistant to infection by the most common forms of HIV‐1. We recently reported on the successful transplantation in an HIV‐1‐positive patient of allogeneic stem cells homozygous for the CCR5‐delta32 allele, which stopped viral replication for more than 27 months without antiretroviral therapy.Here, we report on the results of a meeting regarding the potential implications and future directions of stem cell‐targeted HIV treatments. The meeting drew together an international panel of hematologists, immunologists, HIV specialists and representatives from bone marrow donor registries.The meeting came to an agreement to support further attempts to use CCR5‐delta32 deleted stem cells, for example, prescreened cord blood stem cells, to treat probable HIV‐1‐positive patients with malignancies. Furthermore, improvement of HIV‐1 therapy that interferes with the entry mechanism seems to be a promising approach in HIV‐1‐infected patients with no matching CCR5‐delta32 deleted donor.
Refractory lympho-epithelial carcinoma of the nasopharynx: a case report illustrating a protracted clinical course
Authors: Wu Frederick Y , Yang Eddy S , Willey Christopher D , Ely Kim , Garrett Gaelyn , Cmelak Anthony J 
Published: June 2009

Abstract
Nasopharyngeal carcinoma is an uncommon cancer in North America. Its clinical course is typified by locally advanced disease at diagnosis and has a high propensity for both regional and distant spread. It is, therefore, typically treated with a combination of radiation and chemotherapy. This report describes our 10-year clinical and radiological findings in a 48-year-old Vietnamese male patient with locally-advanced T4N1M0 lympho-epithelial carcinoma of the nasopharynx. Despite a long remission period after his initial course of aggressive chemoradiation, his tumor recurred locally after 4 years. Thereafter, throughout a period of over 10 years, he has been treated with multiple courses of re-irradiation and three different trials of chemotherapy. He was ultimately provided with over 30 months of progression-free tumor control with the epidermal growth factor receptor (EGFR)-inhibitor cetuximab. This case illustrates the commonly protracted course of this disease and its responsiveness to multiple treatment modalities.
Frequent loss of endothelin-3 (EDN3) expression due to epigenetic inactivation in human breast cancer
Authors: Wiesmann Frank , Veeck Jürgen , Galm Oliver , Hartmann Arndt , Esteller Manel , Knüchel Ruth , Dahl Edgar 
Published: June 2009

Abstract
Introduction
Endothelin (EDN) signalling plays a crucial role in cell differentiation, proliferation and migration processes. There is compelling evidence that altered EDN signalling is involved in carcinogenesis by modulating cell survival and promoting invasiveness. To date, most reports have focused on the oncogenic potential of EDN1 and EDN2, both of which are overexpressed in various tumour entities. Here, we aimed at a first comprehensive analysis on EDN3 expression and its implication in human breast cancer.

Methods
EDN3 mRNA expression was assessed by Northern blotting in normal human tissues (n = 9) as well as in matched pairs of normal and tumourous tissues from breast specimens (n = 50). EDN3 mRNA expression in breast cancer was further validated by real-time polymerase chain reaction (PCR) (n = 77). A tissue microarray was used to study EDN3 protein expression in breast carcinoma (n = 150) and normal breast epithelium (n = 44). EDN3 promoter methylation was analysed by methylation-specific PCR in breast cell lines (n = 6) before and after demethylating treatment, normal breast tissues (n = 17) and primary breast carcinomas (n = 128). EDN3 expression and methylation data were statistically correlated with clinical patient characteristics and patient outcome.

Results
Loss of EDN3 mRNA expression in breast cancer, as initially detected by array-based expression profiling, could be confirmed by Northern blot analysis (> 2-fold loss in 96%) and real-time PCR (> 2-fold loss in 78%). Attenuated EDN3 expression in breast carcinoma was also evident at the protein level (45%) in association with adverse patient outcome in univariate (P = 0.022) and multivariate (hazard ratio 2.0; P = 0.025) analyses. Hypermethylation of the EDN3 promoter could be identified as the predominant mechanism leading to gene silencing. Reversion of the epigenetic lock by 5-aza-2'-deoxycytidine and trichostatin A resulted in EDN3 mRNA re-expression in vitro. Furthermore, EDN3 promoter hypermethylation was detected in 70% of primary breast carcinomas with significant association to loss of EDN3 mRNA expression (P = 0.005), whilst normal matched breast tissues revealed no EDN3 promoter methylation.

Conclusions
EDN3 is a frequent target of epigenetic inactivation in human breast cancer, potentially contributing to imbalanced EDN signalling commonly found in this disease. The clinical implication supports the view that EDN3, in contrast to EDN1 and EDN2, may act as natural tumour suppressor in the human mammary gland.
Genomic linkage map of the human blood fluke Schistosoma mansoni
Authors: Criscione Charles D , Valentim Claudia LL , Hirai Hirohisa , LoVerde Philip T , Anderson Timothy JC 
Published: June 2009

Abstract
Background
Schistosoma mansoni is a blood fluke that infects approximately 90 million people. The complete life cycle of this parasite can be maintained in the laboratory, making this one of the few experimentally tractable human helminth infections, and a rich literature reveals heritable variation in important biomedical traits such as virulence, host-specificity, transmission and drug resistance. However, there is a current lack of tools needed to study S. mansoni's molecular, quantitative, and population genetics. Our goal was to construct a genetic linkage map for S. mansoni, and thus provide a new resource that will help stimulate research on this neglected pathogen.

Results
We genotyped grandparents, parents and 88 progeny to construct a 5.6 cM linkage map containing 243 microsatellites positioned on 203 of the largest scaffolds in the genome sequence. The map allows 70% of the estimated 300 Mb genome to be ordered on chromosomes, and highlights where scaffolds have been incorrectly assembled. The markers fall into eight main linkage groups, consistent with seven pairs of autosomes and one pair of sex chromosomes, and we were able to anchor linkage groups to chromosomes using fluorescent in situ hybridization. The genome measures 1,228.6 cM. Marker segregation reveals higher female recombination, confirms ZW inheritance patterns, and identifies recombination hotspots and regions of segregation distortion.

Conclusions
The genetic linkage map presented here is the first for S. mansoni and the first for a species in the phylum Platyhelminthes. The map provides the critical tool necessary for quantitative genetic analysis, aids genome assembly, and furnishes a framework for comparative flatworm genomics and field-based molecular epidemiological studies.
Epac inhibits apoptosis of human leukocytes
Authors: Grandoch M , Bujok V , Fleckenstein D , Schmidt M , Fischer J W , Weber A A 
Published: June 2009

Abstract
Selective activation of Epac proteins inhibits apoptosis in U937, HL-60, and primary human mononuclear cells.
cAMP is known to participate in the regulation of apoptosis in leukocytes. Depending on the cell type, pro- and antiapoptotic effects of cAMP have been described. Thus far, most of the cAMP-dependent effects have been attributed to the activation of PKA. However, Epac proteins (direct cAMP targets and guanine nucleotide exchange factors for Ras-like GTPases) have been shown recently to contribute to cAMP-dependent regulation of apoptosis. Therefore, we investigated the effects of the selective Epac activators 8-pCPT and Sp on apoptosis in human leukocytic cells (U937, HL-60, primary human mononuclear cells). We report here that Epac activation inhibits leukocyte apoptosis significantly.
The functional significance behind expressing two IL–8 receptor types on PMN
Authors: Stillie RoseMarie , Farooq Shukkur Muhammed , Gordon John R , Stadnyk Andrew W 
Published: June 2009

AbstractThe presence of two CXCL8 receptor types combined with the inflammatory roles of PMN has led to interest in whether each receptor type contributes to unique functions.PMN are critical to innate immunity and are fundamental to antibacterial defense. To localize to sites of infection, PMN possess receptors that detect chemoattractant stimuli elicited at the site, such as chemokines, complement split products, or bioactive lipids. Signaling through these receptors stimulates chemotaxis toward the site of infection but also activates a number of biochemical processes, with the result that PMN kill invading bacteria. PMN possess two receptors, CXCR1 and CXCR2, for the N–terminal ELR motif–containing CXC chemokines, although only two chemokine members bind both receptors and the remainder binding only CXCR2. This peculiar pattern in receptor specificity has drawn considerable interest and investigation into whether signaling through each receptor might impart unique properties on the PMN. Indeed, at first glance, CXCR1 and CXCR2 appear to be functionally redundant; however, there are differences. Considering these proinflammatory activities of activating PMN through chemokine receptors, there has been great interest in the possibility that blocking CXCR1 and CXCR2 on PMN will provide a therapeutic benefit. The literature examining CXCR1 and CXCR2 in PMN function during human and modeled diseases will be reviewed, asking whether the functional differences can be perceived based on alterations in the role PMN play in these processes.
DAMPs and inflammatory processes: the role of redox in the different outcomes
Authors: Carta Sonia , Castellani Patrizia , Delfino Laura , Tassi Sara , Venè Roberta , Rubartelli Anna 
Published: June 2009

Abstract
Extracellular redox changes are relevant to the start, progress, and resolution of different acute or chronic inflammatory processes, with emphasis on the modulation of DAMP activity.
Inflammation is deeply entangled with redox modulation. Triggering of PRRs on inflammatory cells induces ROS generation. As a consequence, activated cells mount antioxidant responses to counteract the possible harmful effects of oxidation. Therefore, when repair is completed, homeostasis is restored. Here, we describe some recent results showing that an exuberant antioxidant response to pro–oxidant inflammatory stimuli modifies not only the intra– but also the extracellular redox and contributes to the outcome of the inflammatory process. In particular, the role of redox modulation in IL–1β secretion, in B lymphocyte differentiation to plasma cells, and in tumor progression will be discussed, and the potential consequences of extracellular redox alterations on DAMP activity will be considered.
Antiglucocorticoids in psychiatry
Authors: McIsaac Sean A. , Westrin Åsa , Young Allan H. 
Published: June 2009

SummarySignificant evidence has accrued suggesting that the hypothalamic–pituitary–adrenal (HPA) axis plays a role in some psychiatric disorders. This article reviews the physiology of the HPA axis, evidence of dysfunction in this axis in psychiatric illnesses and the role that this dysfunction might play in pharmacological treatment resistance. Future therapeutic strategies that may potentially arise from these researches are briefly outlined.
The future of specialised alcohol treatment services: a matter of policy?
Authors: Rao Harish , Luty Jason 
Published: June 2009

SummaryAround 7.1 million people in England drink hazardously or harmfully and a further 1.1 million are dependent on alcohol. Motivational interviewing is widely used to treat people with alcohol problems and is probably the best described example of a brief intervention. However, some recent trials have been disappointing. Specialised alcohol treatment services have also suffered from weakness in the evidence base. Investment in treating alcohol misuse has fallen far behind that for drug misuse. The Department of Health's Alcohol Harm Reduction Strategy for England embraces policies that are high-profile and cheap but are ineffective and ignore many effective measures. It recommends stepped care for alcohol treatment, but unlike the equivalent for drugs treatment, it sets no targets and leaves the small (7%) increase in funding to the discretion of local purchasers. UK spending on specialised treatment for drug misuse is estimated to be around £600 million for 2007 – around three times the estimated cost of treatment for alcohol misuse.
Beyond ADHD and narcolepsy: psychostimulants in general psychiatry
Authors: Ng Bradley , O'Brien Angela 
Published: June 2009

SummaryPsychostimulants (dexamphetamine, methylphenidate, modafinil) reduce fatigue, promote alertness and wakefulness, and have possible mood-enhancing properties. In modern psychiatric practice, their use has been limited to attention-deficit hyperactivity disorder and sleep disorders such as narcolepsy. Despite this, research has continued into psychostimulant use in general psychiatry, especially in the treatment of depression and fatigue. This article reviews the recent literature regarding psychostimulant use in general and consultation-liaison psychiatry. Although psychostimulants continue to attract clinical research, there is currently not enough evidence to recommend their routine use for general psychiatric conditions.
Anger and depression
Authors: Busch Fredric N. 
Published: June 2009

SummaryA series of psychoanalytic theorists and clinicians have suggested that conflicts about anger play a central role in the development of depression. Research data have supported the notion that patients struggle with the experience and expression of angry feelings. Anger in people with depression often stems from narcissistic vulnerability, a sensitivity to perceived or actual loss or rejection. These angry reactions cause intrapsychic conflicts through the onset of guilt and the fear that angry feelings will disrupt relationships. These conflicts lead to anger being directed inwards, further lowering self-esteem, creating a vicious cycle. Defence mechanisms that are triggered, including passive aggression, reaction formation, denial and identification with the aggressor, are ineffective at managing these conflicts and further prevent the appropriate expression of anger. This article discusses how to identify and detoxify angry feelings and fantasies using a psychodynamic approach.
Mood disorders and violence: a new focus
Authors: Oakley Clare , Hynes Fiona , Clark Tom 
Published: June 2009

SummaryViolent behaviour in people with a psychiatric disorder causes great public concern and leads to stigma for people with mental illness. There is good evidence for a correlation between schizophrenia and increased rates of violence but any association between mood disorders and violence has been comparatively overlooked. It appears that there may be more evidence relating mood disorders and violence than many clinicians realise. This article highlights the difficulties in assessing this, summarises what is known and discusses what this means for clinical practice.
Targeting the HPA axis in major depression: does it work?
Authors: Claes Stephan 
Published: June 2009

SummaryIn the search for antidepressant drugs with enhanced efficacy, targeting the hypothalamic–pituitary–adrenal (HPA) axis is a valid strategy. This commentary critically summarises the evidence for the efficacy of antidepressant drugs targeting the HPA axis, and concludes that the available clinical trials do not support claims that this class of drugs is superior to existing treatments.
Patterns of neurocognitive impairment in first-episode bipolar
disorder and schizophrenia
Authors: Barrett Suzanne L. , Mulholland Ciaran C. , Cooper Stephen J. , Rushe Teresa M. 
Published: June 2009

BackgroundResearching psychotic disorders in unison rather than as separate
diagnostic groups is widely advocated, but the viability of such an
approach requires careful consideration from a neurocognitive
perspective.AimsTo describe cognition in people with bipolar disorder and schizophrenia
and to examine how known causes of variability in individual's
performance contribute to any observed diagnostic differences.MethodNeurocognitive functioning in people with bipolar disorder
(n = 32), schizophrenia (n = 46) and
healthy controls (n = 67) was compared using analysis of
covariance on data from the Northern Ireland First Episode Psychosis
Study.ResultsThe bipolar disorder and schizophrenia groups were most impaired on tests
of memory, executive functioning and language. The bipolar group
performed significantly better on tests of response inhibition, verbal
fluency and callosal functioning. Between-group differences could be
explained by the greater proclivity of individuals with schizophrenia to
experience global cognitive impairment and negative symptoms.ConclusionsParticular impairments are common to people with psychosis and may prove
useful as endophenotypic markers. Considering the degree of individuals'
global cognitive impairment is critical when attempting to understand
patterns of selective impairment both within and between these diagnostic
groups.
Research as part of the career of a psychiatrist entering clinical practice
Authors: Fogel Joshua 
Published: June 2009

SummaryThis article reviews the literature on research as part of the career of a psychiatrist. Many of the reviewed articles emphasised an interest among psychiatry trainees for conducting psychiatric research. A number of reviewed articles discussed the aspects of research training experiences that lead to a career with a major research emphasis. A few articles described the percentage of time dedicated to research by academic psychiatrists. for those trainees completing their training and who plan to pursue a career as a clinician, there are still ways to incorporate research into clinical practice and continue to maintain some of the research skills that were learned as a psychiatry trainee.
Service user perspectives on the content of the undergraduate curriculum in psychiatry
Authors: Dogra Nisha , Cavendish Sue , Anderson Jill , Edwards Ruth 
Published: June 2009

Aims and MethodTo explore user perspectives on the content and delivery of the undergraduate curriculum in psychiatry. the study design was qualitative and used focus groups. Four focus groups were run with a total of 28 participants.ResultsThe key finding was that participants were clearer about the attitudes they felt students should convey than they were about the skills and knowledge required.Clinical ImplicationsService user perspectives on the content of the undergraduate psychiatry curriculum need to be considered as curricula are developed.
Losing participants before the trial ends erodes credibility of findings
Authors: Xia Jun , Adams Clive , Bhagat Nishant , Bhagat Vinaya , Bhoopathi Paranthaman , El-Sayeh Hany , Pinfold Vanessa , Takriti Yahya 
Published: June 2009

Aims and MethodTo estimate the proportion of attrition at which results of drug trials for people with schizophrenia lose enough credibility to become mistrusted by relevant groups of stakeholders. A piloted questionnaire was sent to 128 local clinicians, 100 relevant researchers and 104 service users and carers.ResultsWe received the biggest number of responses from the service user and carer group (n=81, 76%); 43% of clinicians and 32% of researchers responded. All three groups suggested that the follow-up rate for a 12-week schizophrenia drug trial should be around 70–75% for the trial to be credible.Clinical ImplicationsThis survey suggests that relevant stakeholders, including researchers, fundamentally mistrust results of the majority of drug trials in schizophrenia. Adopting a more pragmatic trial design can help address this.