Venous leg ulceration: skin and serum zinc concentrations.

Zinc was measured in serum and in thigh skin in patients with venous leg ulceration and also in controls. Skin zinc concentrations were expressed in terms of area and dry weight. The mean serum zinc concentration was significantly lowered in the ulcer group. The thigh skin zinc concentration was elevated in patients with chronic venous leg ulceration. The difference was more marked if the zinc concentration was calculated per surface area of skin, but did not reach statistical significance.     

The expression of immunoglobulin determinants on the surface of antigen-binding lymphoid cells in mice. II. Allotypes of the lg-1 locus

Inhibition of rosette-forming cells by anti-immunoglobulin sera has been used as a model system to investigate the phenotypic expression of IgG_2a allotypes on the surface of mouse spleen cells reactive against sheep erythrocyte antigens. The evidence presented suggests that reactive cells from mice heterozygous at the Ig-1 locus may not be restricted to the expression of the product of only one parental allele on their surface. Control studies with mixtures of cells from mice compatible with respect to H-2 antigens but differing at the Ig-1 locus suggest that this finding is not the result of a passive absorption phenomenon. This apparent lack of allellic exclusion was demonstrated with cells harvested during the early part of the response to a primary injection of antigen. Reactive cells later in the immune response appeared to be restricted to the expression of one parental allotype.     

National Dementia Strategy: well intentioned — but how well founded and how well directed?

The National Dementia Strategy was published in February 2009. It was eagerly anticipated and has generated a good deal of sustained media interest, widened awareness, and heightened expectation of better help for people with dementia. The three ambitions of the strategy — to raise awareness, facilitate assessment, and improve services — are unquestionably correct; but the assumptions, emphases, and economic predictions are questionable. Encouraging reliance on referral to secondary care centres, and exaggerated claims for the effectiveness of interventions to achieve clinical improvement and cost savings, may lead to disappointment and frustration. The infrastructure of care and treatment of people throughout the course of dementia will be better informed and delivered by a collaborative model which respects the knowledge and commitment contained within families and primary care. Better services will require substantial redirection of resources.     

A guide to understanding the steroid pathway: New insights and diagnostic implications

Steroid analysis has always been complicated requiring a clear understanding of both the clinical and analytical aspects in order to accurately interpret results. The literature relating to this specialised area spans many decades and the intricacies of the steroid pathway have evolved with time. A number of key changes, including discovery of the alternative androgen pathway, have occurred in the last decade, potentially changing our understanding and approach to investigating disorders of sexual development. Such investigation usually occurs in specialised paediatric centres and although preterm infants represent only a small percentage of the patient population, consideration of the persistence of the foetal adrenal zone is an additional important consideration when undertaking steroid hormone investigations. The recent expanded role of mass spectrometry and molecular diagnostic methods provides significant improvements for accurate steroid quantification and identification of enzyme deficiencies. However analysis of steroids and interpretation of results remain complicated. This review aims to provide an insight into the complexities of steroid measurement in children and offers an updated guide to interpretation, of serum and urine steroids through the presentation of a refined steroid pathway.     

Beyond competence: defining and promoting excellence in anaesthesia

Recent trends in medical training have tended to focus on competence, in the sense of adequate performance, rather than excellence. This article reviews published literature and relevant concepts relating to excellence and professionalism from within anaesthesia, from medicine more generally and from outside the profession. A number of conceptual frameworks are presented that could be adapted for the promotion of excellence, and some of the necessary prerequisites for this promotion discussed.     

Men’s business,women’s work: gender influences and fathers’ smoking

To further understand men’s continued smoking during their partner’s pregnancy and the postpartum period, a study was undertaken to explore women’s perspectives of men’s smoking. Using a gender lens, a thematic analysis of transcribed interviews with 27 women was completed. Women’s constructions of men’s smoking and linkages to masculine and feminine ideals are described. The findings highlight the ways women position themselves both as defenders and regulators of men’s smoking. Femininities that aligned women with hegemonic masculine principles underpinned their roles in relation to men’s smoking and presented challenges in influencing their partner’s tobacco reduction. By positioning the decision to quit smoking as a man’s solitary pursuit, women reduced potential relationship conflict and managed to maintain their identity as a supportive partner. Insights from this study provide direction for developing gender‐specific tobacco reduction initiatives targeting expectant and new fathers. Indeed, a lack of intervention aimed at encouraging men’s tobacco reduction has the potential to increase relationship tensions, and inadvertently maintain pressure on women to regulate fathers’ smoking. This study illustrates how gender‐based analyses can provide new directions for men’s health promotion programmes and policies.     

Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia

Children with Down syndrome (DS) have a greatly increased risk of acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia (ALL). Both DS-AMKL and the related transient myeloproliferative disorder (TMD) have GATA1 mutations as obligatory, early events. To identify mutations contributing to leukemogenesis in DS-ALL, we undertook sequencing of candidate genes, including FLT3, RAS, PTPN11, BRAF, and JAK2. Sequencing of the JAK2 pseudokinase domain identified a specific, acquired mutation, JAK2R683, in 12 (28%) of 42 DS-ALL cases. Functional studies of the common JAK2R683G mutation in murine Ba/F3 cells showed growth factor independence and constitutive activation of the JAK/STAT signaling pathway. High-resolution SNP array analysis of 9 DS-ALL cases identified additional submicroscopic deletions in key genes, including ETV6, CDKN2A, and PAX5. These results infer a complex molecular pathogenesis for DS-ALL leukemogenesis, with trisomy 21 as an initiating or first hit and with chromosome aneuploidy, gene deletions, and activating JAK2 mutations as complementary genetic events.