Background:Chronic fatigue syndrome (CFS) is a multisystem disease, the pathogenesis of which remains undetermined.Aims:To test the hypothesis that there are reproducible abnormalities of gene expression in patients with CFS compared with normal healthy persons.Methods:To gain further insight into the pathogenesis of this disease, gene expression was analysed in peripheral blood mononuclear cells from 25 patients with CFS diagnosed according to the Centers for Disease Control criteria and 25 normal blood donors matched for age, sex, and geographical location, using a single colour microarray representing 9522 human genes. After normalisation, average difference values for each gene were compared between test and control groups using a cutoff fold difference of expression ⩾ 1.5 and a p value of 0.001. Genes showing differential expression were further analysed using Taqman real time polymerase chain reaction (PCR) in fresh samples.Results:Analysis of microarray data revealed differential expression of 35 genes. Real time PCR confirmed differential expression in the same direction as array results for 16 of these genes, 15 of which were upregulated (ABCD4, PRKCL1, MRPL23, CD2BP2, GSN, NTE, POLR2G, PEX16, EIF2B4, EIF4G1, ANAPC11, PDCD2, KHSRP, BRMS1, and GABARAPL1) and one of which was downregulated (IL-10RA). This profile suggests T cell activation and perturbation of neuronal and mitochondrial function. Upregulation of neuropathy target esterase and eukaryotic translation initiation factor 4G1 may suggest links with organophosphate exposure and virus infection, respectively.Conclusion:These results suggest that patients with CFS have reproducible alterations in gene regulation.

Current controlled trials, http://www.controlled-trials.com/, ISRCTN09712705.

BackgroundDecisions regarding the hospitalisation of nursing home residents may present a difficult dilemma for GPs. There are pressures to admit very frail patients with exacerbations of illness even though such frailty may limit the possible health gains. As 'gatekeepers' to NHS, GPs are expected to make best use of resources and may be criticised for 'inappropriate' admissions. Little is understood about the influences on GPs as they make such decisions AimTo explore GPs views on factors influencing decisions on admitting frail nursing home residents to hospital. Design and settingA purposive sample of 21 GPs from two counties in the South of England. MethodData from semi-structured, one-to-one interviews with GPs were analysed using thematic analysis following principles of the constant comparative method. ResultsThis study suggests that while clinical assessment, perceived benefits and risks of admission, and patients' and relatives' preferences are key factors in determining admissions, other important factors influencing decision making include medico-legal concerns, communications, capability of nursing homes and GP workload. These factors were also perceived by GPs as influencing the feasibility of keeping patients in the nursing home when this was clinically appropriate. Key areas suggested by GPs to improve practice were improving communication (particularly informational continuity), training and support for nursing staff, and peer support for GPs. Local initiatives to address these issues were very variable. ConclusionDeveloping a systematic palliative care approach to address poor documentation and communication, the capability of nursing homes, and medico-legal concerns has the potential to improve decision-making regarding hospital admissions.

The findings do not support a specific therapeutic effect for BioBran in CFS. The improvement showed by both groups over time highlights the importance of placebo controls when evaluating interventions in CFS.

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Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of at least 6 months duration, which is accompanied by various rheumatological, infectious and neuropsychiatric symptoms. A collaborative study group has been formed to deal with the current areas for development in CFS research—namely, to develop an understanding of the molecular pathogenesis of CFS, to develop a diagnostic test and to develop specific and curative treatments. Various groups have studied the gene expression in peripheral blood of patients with CFS, and from those studies that have been confirmed using polymerase chain reaction (PCR), clearly, the most predominant functional theme is that of immunity and defence. However, we do not yet know the precise gene signature and metabolic pathways involved. Currently, this is being dealt with using a microarray representing 47 000 human genes and variants, massive parallel signature sequencing and real-time PCR. It will be important to ensure that once a gene signature has been identified, it is specific to CFS and does not occur in other diseases and infections. A diagnostic test is being developed using surface-enhanced, laser-desorption and ionisation-time-of-flight mass spectrometry based on a pilot study in which putative biomarkers were identified. Finally, clinical trials are being planned; novel treatments that we believe are important to trial in patients with CFS are interferon-β and one of the anti-tumour necrosis factor-α drugs.

GP referral to a specialist service appeared to be highly valued by the participants in this study. The levels of uncertainty expressed by many patients about the nature of CFS/ME raises the issue of the role of information on CFS/ME during the early stages of the illness and suggests a need for more reassurance and positive advice during the waiting period.