Insulin resistance in polycystic ovary syndrome is associated with defective regulation of ERK1/2 by insulin in skeletal muscle in vivo.

Insulin resistance is a recognized feature of PCOS (polycystic ovary syndrome). However, the molecular reason(s) underlying this reduced cellular insulin sensitivity is not clear. The present study compares the major insulin signalling pathways in skeletal muscle isolated from PCOS and controls. We measured whole-body insulin sensitivity and insulin signalling in skeletal muscle biopsies taken before and after acute exposure to hyperinsulinaemia in nine women diagnosed with PCOS and seven controls. We examined the expression, basal activity and response to in vivo insulin stimulation of three signalling molecules within these human muscle samples, namely IRS-1 (insulin receptor substrate-1), PKB (protein kinase B) and ERK (extracellular-signal-regulated kinase) 1/2. There was no significant difference in the expression, basal activity or activation of IRS-1 or PKB between PCOS and control subjects. However, there was a severe attenuation of insulin stimulation of the ERK pathway in muscle from all but two of the women with PCOS (the two most obese), and an accompanying trend towards higher basal phosphorylation of ERK1/2 in PCOS. These results are striking in that the metabolic actions of insulin are widely believed to require the IRS-1/PKB pathway rather than ERK, and the former has been reported as defective in some previous PCOS studies. Most importantly, the molecular defect identified was independent of adiposity. The altered response of ERK to insulin in PCOS was the most obvious signalling defect associated with insulin resistance in muscle from these patients.

Can we improve recruitment of oocyte donors with loss of donor anonymity? A hospital-based survey.

BACKGROUND: Loss of donor anonymity, as a result of an amendment to the Human Fertilisation and Embryology Act 1990, has led to concerns regarding continued recruitment of gamete and embryo donors. This survey aims to examine the impact of loss of anonymity on willingness to donate oocytes and strategies to improve recruitment. METHODS: Five hundred anonymous self-report questionnaires were randomly allocated to hospital staff between September and December 2004. MAIN OUTCOME MEASURES: To determine public awareness of gamete donation, preferred information sources for potential donors, and affect of loss of anonymity on willingness to consider gamete donation. RESULTS: One hundred and sixty-six responses (33%) were received. Only female respondents (n=143) were analysed. Awareness of gamete donation was high (90%), with 34% willing to consider donation. Removal of donor anonymity reduced this figure to 17%. For women under 35 years of age, the corresponding figures are 43% and 19%, respectively. Potential donors may utilize multiple sources of information prior to reaching a decision about donation. CONCLUSIONS: Loss of donor anonymity reduced by half those willing to consider donation in all age groups. The future of this service depends on recruitment of donors willing to be identified. Consideration of older donors may be an option if adequate counselling occurs.

Latency of onset of de novo myelodysplastic syndromes.

The latency of onset of de novo myelodysplastic syndromes (MDS) is unknown. We report a retrospective analysis of blood counts from patients with MDS and acute myeloid leukemia (AML), and demonstrate temporal differences in rates of change of hemoglobin concentration and mean cell volume within 2-3 years of diagnosis, indicative of the earliest evidence of disease.

Asthma or COPD? An inwestigation into the symptom patterns of asthma may highlight the need for more rigorous diagnostic procedures in elderly patients.

AIM: To investigate the symptom patterns of elderly patients registered as active asthmatics. METHOD: An observational study using a database of 393 practices from throughout the United Kingdom. Participating practices provided health-service resource-use and symptom data for 30 randomly selected asthma patients. 8,244 adults, (16+ years), were stratified into three age groups, 4315(52%) aged 16-44, 2339(28%) 45-64, and 1590(19%) 65+. Comparisons were made for management and outcome measures (attack incidence, symptoms, health service resource use, drug therapies) between the groups. RESULTS: Patients over 64 years old experienced more morning and exercise symptoms(p<0.001) and had more hospital admissions(p<0.001). They received higher levels of medication(p<0.001), were more compliant(p<0.001), but had poorer inhaler technique(p<0.001). CONCLUSION: Despite higher medication levels, 1,164(73%) patients over 64 years reported symptoms, 430(37%) of these, daily. For older patients, where regular symptoms are present despite high medication levels, investigation for diagnoses other than asthma should be routine.