Managing invasive fungal disease in immunocompromised patients.

Celebrating its 30th anniversary in Budapest this year, the International Immunocompromised Host Society (ICHS) was established to advance the understanding of interactions between host defenses and microbial agents in order to improve the prevention and management of human disease in patients with compromised immune function. Much has been achieved in the intervening years, and presentations on the challenges of invasive fungal disease at this year's ICHS congress reflected the changing nature of the population at risk of fungal disease, the growing range of fungal pathogens, and evolving approaches to the prevention, diagnosis and treatment of fungal infection.

Managing invasive fungal infection in hematopoietic stem-cell transplantation.

Reduced intensity conditioning regimens and a wider range of donor sources, including cord blood, mean that more patients can be offered potentially curative allogeneic hematopoietic stem cell transplantation than ever before. Although these modalities aim to reduce procedure-related morbidity and mortality, their potential benefit may be overshadowed by a changing spectrum of problems related to the immunocompromised status of affected patients. Acute or chronic extensive graft-versus-host disease, which occasionally emerges in the late post-transplant period, and prolonged neutropenia due to delayed engraftment still carry a substantial risk of invasive fungal and other infections. As a result, advances in antifungal prophylaxis and pre-emptive treatment were widely reported at the 36th Annual Meeting of the European Group for Blood and Marrow Transplantation attended this year by approximately 3800 delegates.

New boundaries for lymphatic mapping-report of the Fifth International Sentinel Node Conference.

The Fifth Biennial International Sentinel Node Society meeting was held in Rome from 1 to 4 November 2006. Compared with previous meetings, there was a shift in focus from aspects of the clinical technique of the procedure to aspects of basic science that indicate the biology of the disease. The authors report on conference presentations relating to melanoma, including discussion of results from the Multicentre Selective Lymphadenectomy Trial 1 in intermediate thickness primary melanoma.

Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37.

The sole human cathelicidin peptide, LL-37, has been demonstrated to protect animals against endotoxemia/sepsis. Low, physiological concentrations of LL-37 (< or =1 microg/ml) were able to modulate inflammatory responses by inhibiting the release of the proinflammatory cytokine TNF-alpha in LPS-stimulated human monocytic cells. Microarray studies established a temporal transcriptional profile and identified differentially expressed genes in LPS-stimulated monocytes in the presence or absence of LL-37. LL-37 significantly inhibited the expression of specific proinflammatory genes up-regulated by NF-kappaB in the presence of LPS, including NFkappaB1 (p105/p50) and TNF-alpha-induced protein 2 (TNFAIP2). In contrast, LL-37 did not significantly inhibit LPS-induced genes that antagonize inflammation, such as TNF-alpha-induced protein 3 (TNFAIP3) and the NF-kappaB inhibitor, NFkappaBIA, or certain chemokine genes that are classically considered proinflammatory. Nuclear translocation, in LPS-treated cells, of the NF-kappaB subunits p50 and p65 was reduced > or =50% in the presence of LL-37, demonstrating that the peptide altered gene expression in part by acting directly on the TLR-to-NF-kappaB pathway. LL-37 almost completely prevented the release of TNF-alpha and other cytokines by human PBMC following stimulation with LPS and other TLR2/4 and TLR9 agonists, but not with cytokines TNF-alpha or IL-1beta. Biochemical and inhibitor studies were consistent with a model whereby LL-37 modulated the inflammatory response to LPS/endotoxin and other agonists of TLR by a complex mechanism involving multiple points of intervention. We propose that the natural human host defense peptide LL-37 plays roles in the delicate balancing of inflammatory responses in homeostasis as well as in combating sepsis induced by certain TLR agonists.

Cancer care. Palliative care. The last days of care.

The government has promised a further 12m pounds over three years for end-of-life care, on top of the 50m pounds a year for palliative care. A framework developed by Macmillan Cancer Relief has identified seven gold standards of care including communication, coordination, control of symptoms, carer support and care in the dying phase. The government has committed to doubling the number of palliative care consultants by 2015.

Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action.

Methods to systematically test drugs against all possible proteins in a cell are needed to identify the targets underlying their therapeutic action and unwanted effects. Here, we show that a genome-wide drug-induced haploinsufficiency screen by using yeast can reveal drug mode of action in yeast and can be used to predict drug mode of action in human cells. We demonstrate that dihydromotuporamine C, a compound in preclinical development that inhibits angiogenesis and metastasis by an unknown mechanism, targets sphingolipid metabolism. The systematic, unbiased and genome-wide nature of this technique makes it attractive as a general approach to identify cellular pathways affected by drugs.

Contemporary thinking in stroke prevention and management.

Stroke is the third largest cause of death in the UK, after heart disease and cancer, and the largest single cause of severe adult disability (Stroke Association, 2003). Specialist and consultant stroke nurses are playing a growing role in rapid assessment clinics and acute care, as well as in coordinating rehabilitation and other follow-up services, including secondary prevention clinics. Health promotion to reduce the risk of stroke is also an important consideration and an area where nurses can play a leading role. Risk prevention measures and behaviours include physical activity, and cutting down on smoking and alcohol intake. A healthy diet is also a major factor in reducing stroke risk. This year Stoke Awareness Week, which starts on 29 September, is focusing on the importance of eating a colourful variety of fruit and vegetables, with the message: 'Eat a rainbow. Beat a stroke'.