Fertility and sexual function in long-term survivors of haematological malignancy: using patient-reported outcome measures to assess a neglected area of need in the late effects clinic.

Problems of sexual function and fertility in long-term survivors (≥5 years) of haematological malignancy are often neglected in clinic. Our centre carried out a questionnaire study in this population addressing patient-perceived fertility and sexual function. 718 patients responded (56% of those invited; 39% Hodgkin, 45% non-Hodgkin lymphoma, 16% acute leukaemia).

Investigating the genetic variation underlying episodicity in major depressive disorder: suggestive evidence for a bipolar contribution.

Background: Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD.

Methods: Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies.

Latency can be conferred to a variety of cytokines by fusion with latency-associated peptide from TGF-β.

Objectives: Targeting cytokines to sites of disease has clear advantages because it increases their therapeutic index. We designed fusion proteins of the latent-associated peptide (LAP) derived from TGF-β with various cytokines via a matrix metalloproteinase (MMP) cleavage site. This design confers latency, increased half-life and targeting to sites of inflammation.

Genome-wide analysis of blood pressure variability and ischemic stroke.

Background And Purpose: Visit-to-visit variability in blood pressure (vBP) is associated with ischemic stroke. We sought to determine whether such variability has genetic causes and whether genetic variants associated with BP variability are also associated with ischemic stroke.

Methods: A Genome Wide Association Study (GWAS) for loci influencing BP variability was undertaken in 3802 individuals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study, in which long-term visit-to-visit and within-visit BP measures were available.

Enhanced vasodilator activity of nitrite in hypertension: critical role for erythrocytic xanthine oxidoreductase and translational potential.

Elevation of circulating nitrite (NO2(-)) levels causes vasodilatation and lowers blood pressure in healthy volunteers. Whether these effects and the underpinning mechanisms persist in hypertension is unknown. Therefore, we investigated the consequences of systemic nitrite elevation in spontaneously hypertensive rats and conducted proof-of-principle studies in patients.

Impact of asthma on educational attainment in a socioeconomically deprived population: a study linking health, education and social care datasets.

Background: Asthma has the potential to adversely affect children's school examination performance, and hence longer term life chances. Asthma morbidity is especially high amongst UK ethnic minority children and those experiencing social adversity, populations which also have poor educational outcomes. We tested the hypothesis that asthma adversely affects performance in national school examinations in a large cohort from an area of ethnic diversity and social deprivation.

Distinct endothelial pathways underlie sexual dimorphism in vascular auto-regulation.

Background And Purpose: Pre-menopausal females have a lower incidence of cardiovascular disease compared with age-matched males, implying differences in the mechanisms and pathways regulating vasoactivity. In small arteries, myogenic tone (constriction in response to raised intraluminal pressure) is a major determinant of vascular resistance. Endothelium-derived dilators, particularly NO, tonically moderate myogenic tone and, because the endothelium is an important target for female sex hormones, we investigated whether NO-mediated moderation of myogenic tone differed between the sexes.

20-Hydroxyeicosatetraenoic acid (20-HETE) is a novel activator of transient receptor potential vanilloid 1 (TRPV1) channel.

TRPV1 is a member of the transient receptor potential ion channel family and is gated by capsaicin, the pungent component of chili pepper. It is expressed predominantly in small diameter peripheral nerve fibers and is activated by noxious temperatures >42 °C. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 4A/4F-derived metabolite of the membrane phospholipid arachidonic acid.

Amplified segment in the 'Down syndrome critical region' on HSA21 shared between Down syndrome and euploid AML-M0 excludes RUNX1, ERG and ETS2.

Children with Down syndrome have a 20- to 50-fold increased risk of acute lymphocytic or myeloid leukaemia. Whole or partial gains of chromosome 21 have been described in multiple childhood leukaemias, and have recently been reported as a likely primary event in B-precursor-acute lymphoblastic leukaemia. It is unclear which amplified gene(s) on chromosome 21 play a key role in leukaemia progression.

Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice.

Females are protected against mortality arising from severe sepsis; however, the precise mechanisms that confer this survival advantage in females over males are unclear. Resident leukocytes in resting tissues have a significant influence on circulating cytokine levels and recruitment of blood leukocytes during acute inflammatory responses. Whether the phenotype of resident leukocytes is distinct in females is unknown.

Shadowing a foundation-year doctor: a third-year medical student's perspective.

Context: This paper considers the advantages of shadowing foundation-year doctors (FY1) in the third year of medical school, an opportunity the UK's General Medical Council (UKGMC) recommends to be given to final-year students only.

Method: Eighteen students spent 1 day each shadowing an FY1, holding their pager and carrying out their duties under direct supervision. Questionnaires, based on UKGMC expectations of an FY1, were completed assessing students' confidence and experience before and after the shifts.

Evaluation of two molecular assays for rapid detection of mycobacterium tuberculosis resistance to fluoroquinolones in high-tuberculosis and -multidrug-resistance Settings.

The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of drug resistance, including multidrug and extensive drug resistance to TB (M/XDRTB). Rapid diagnosis of resistance to fluoroquinolones (FQs) using molecular assays is essential for the implementation of appropriate drug regimens and prevention of the transmission of XDR strains. A total of 51 individual MDRTB strains were tested by pyrosequencing of the quinolone resistance determining region of the gyrA gene and the GenoType MTBDRsl assay (Hain Lifescience, GmbH, Nehren, Germany), and the results were evaluated against those obtained by phenotypic drug susceptibility testing (DST).

Oedema in obesity; role of structural lymphatic abnormalities.

Oedema is a common finding in obesity and its cause is not always clear. Possible causes include impairment of cardiac, respiratory and/or renal function, chronic venous insufficiency and lymphatic problems. Lymphoscintigraphy is the best method to detect structural lymphatic abnormalities that can cause lymphoedema.

Diagnosis and localisation of insulinoma: the value of modern magnetic resonance imaging in conjunction with calcium stimulation catheterisation.

Context: Preoperative localisation of insulinoma improves cure rate and reduces complications, but may be challenging.

Objective: To review diagnostic features and localisation accuracy for insulinomas.

Design: Cross-sectional, retrospective analysis.

From IL-15 to IL-33: the never-ending list of new players in inflammation. Is it time to forget the humble aspirin and move ahead?

The study of the inflammatory response has seen a tremendous expansion over the last 30 years. Advancements in technology and better knowledge of the ethiopathogenesis of several inflammatory conditions have facilitated this process allowing researchers to almost reach the core of problem. Thus, we now know that inflammation can be manifested in many different ways depending on the context that has elicited it.

On the adaptive nature of annexin-A1.

Studies over the last decade have provided us with a wealth of evidence showing that Annexin-1 is a homeostatic endogenous anti-inflammatory mediator of the innate immune system. However, as in Robert Louis Stevenson's novel 'The Strange Case of Dr Jekyll and Mr Hyde', recent investigations on the role of this protein in the adaptive immune response have revealed a previous unknown 'dark side' as positive modulator of T cell activation. This review will be focusing on these recent findings providing further evidences for the promising therapeutic potential of drugs targeting Annexin-1.

The age distribution of self-reported personality disorder traits in a household population.

Stability over time is an essential criterion for the diagnosis of a personality disorder (PD) according to DSM-IV and ICD-10. However, both longitudinal and cross-sectional studies have demonstrated considerable changes of personality disorder traits during life-span, an observation which challenges this assumption. We measured self-reported DSM-IV personality disorder traits in a nationally representative community sample using a cross-sectional design.

Psychopathy among prisoners in England and Wales.

Most research into psychopathy among prisoners is based on selected samples. It remains unclear whether prevalences are lower among European populations. This study aimed to measure the prevalence of psychopathy, and the distribution and correlates of psychopathic traits in a representative national sample of prisoners.

Prevalence and correlates of psychopathic traits in the household population of Great Britain.

There are no previous surveys of psychopathy and psychopathic traits in representative general population samples using standardized instruments. This study aimed to measure prevalence and correlates of psychopathic traits, based on a two-phase survey using the Psychopathy Checklist: Screening Version (PCL: SV) in 638 individuals, 16-74 years, in households in England, Wales and Scotland. The weighted prevalence of psychopathy was 0.

The role of immune suppression and HHV-8 in the increasing incidence of HIV-associated multicentric Castleman's disease.

Background: In HIV cohorts with access to highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) is falling; however, the incidence of multicentric Castleman's disease (MCD) in HIV has not previously been described.

Methods: The incidence of HIV-associated MCD was calculated from a prospective HIV database with 56 202 patient-years of follow-up and compared with KS. Univariate and multivariate analyses were carried out to identify factors associated with MCD.

Banding in F2 general practice posts.

There are educational benefits in Foundation Year 2 general practice postsJunior doctors experienced financial difficulties from the lack of banding payments in these postsLow payment is a disincentive for doctors when choosing their rotationsChanges made to the working hours and the antisocial nature of the posts may qualify doctors for higher banding.

Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles.

Polymorphonuclear leukocyte (PMN)-derived microparticles display inhibitory properties on target cells as assessed in vitro; since PMNs contain abundant amounts of the endogenous anti-inflammatory protein annexin 1 (AnxA1), we tested here whether biologically active AnxA1 could be present in PMN-derived microparticles. PMN adhesion to human umbilical vein endothelial cell (HUVEC) monolayers led to the generation of microparticles that contained AnxA1, as detected by Western blotting, flow cytometry, and mass spectrometry analyses. Addition of these microparticles to recipient PMNs prior to flow over HUVEC monolayers significantly inhibited cell adhesion, an effect abrogated by a neutralizing anti-AnxA1 antibody, or an antibody raised against the AnxA1 receptor, that is termed lipoxin A(4) receptor or ALX.

Asthma year in review 2006-7.

This review focuses on papers published between September 2006 and September 2007 that either answer important clinical questions, or signpost important areas for future research.