Objective Impaired awareness of hypoglycaemia (IAH) is a major risk factor for severe hypoglycaemia in Type 1 diabetes. Although biochemical hypoglycaemia is asserted to be more frequent in IAH, this has not been estimated accurately. The aim of this study was to use Continuous Glucose Monitoring (CGM) to quantify hypoglycaemia in IAH and evaluate its use in identifying impaired awareness of hypoglycaemia.Methods Ninety-five patients with Type 1 diabetes were classified as having normal (n = 74) or impaired awareness (n = 21) using an established method of assessing hypoglycaemia awareness. Hypoglycaemia exposure was assessed prospectively over 9-12 months using weekly 4-point capillary home blood glucose monitoring (HBGM), 5 days of CGM and prospective reporting of severe hypoglycaemia. The frequencies of biochemical and severe hypoglycaemia were compared in patients with normal and impaired awareness of hypoglycaemia.Results Patients with impaired awareness had a 3-fold higher incidence of severe hypoglycaemia than those with normal awareness [incidence rate ratio (IRR) 3.37 (95% CI 1.30-8.7); P = 0.01] and 1.6-fold higher incidence of hypoglycaemia on weekly HBGM [IRR 1.63 (95% CI 1.09-2.44); P = 0.02]. No significant differences were observed with CGM [IRR for sensor glucose £ 3.0 mmol ⁄ l 1.47 (95% CI 0.91-2.39); P = 0.12; IRR for sensor glucose £ 2.2 mmol ⁄ l 1.23 (95% CI 0.76-1.98); P = 0.40].Conclusions Patients with Type 1 diabetes with impaired awareness had a 3-fold higher risk of severe hypoglycaemia and 1.6-fold higher incidence of biochemical hypoglycaemia measured with weekly glucose monitoring compared with normal awareness, but 5 days of CGM did not differentiate those with impaired from those with normal awareness.Diabet. Med. 27, 666-672 (2010)

In the UK there are limited data about university students' risky sexual behaviour. A cross-sectional web-survey was conducted to investigate factors associated with high-risk sex among students at two UK universities. High-risk sex was reported by 25% of 1108. High personal sexually transmitted infection (STI) risk perception and permissive attitudes towards casual sex were associated with high-risk sex for both men (odds ratio [OR]: 12.12; 95% confidence interval [CI]: 4.10-35.81; OR: 2.49; 95%CI: 1.11-5.56, respectively) and women (OR: 22.31; 95% CI: 9.34-53.26; OR: 3.02; 95% CI: 1.82-5.01, respectively). For men, drinking alcohol (OR: 17.67; 95% CI: 1.90-164.23) and for women age and frequent drinking (OR: 2.02; 95% CI: 1.05-3.89; OR: 1.89; 95% CI: 1.08-3.31, respectively) were associated with high-risk sex. However, perceiving an average student as more likely to contract STIs (men, OR: 0.34; 95% CI: 0.16-0.75) or HIV (men, OR: 0.44; 95% CI: 0.20-0.96; women, OR: 0.42; 95% CI: 0.28-0.63) and finding it difficult to discuss sexual matters (women, OR: 0.60; 95% CI: 0.39-0.91) were negatively associated with high-risk sex. Most of the factors found were similar to other populations, but some psychosocial factors showed complex patterns of association that require further investigation.

Endothelial dysfunction caused by the early atherosclerotic process or by endothelial exposure to atherogenic lipids, including lysophosphatidylcholine (lysoPC), is characterized by a selective impairment of responses mediated by the pertussis toxin-sensitive Gi-2 protein. Experiments were performed to analyze the mechanisms underlying this effect. Bradykinin (BK: Gi-2 protein-independent), serotonin (5-HT: Gi-2 protein-dependent), or direct activation of the G(i-2)-protein by mastoparan increased the release of endothelium-derived nitric oxide (EDNO) from porcine arterial endothelial cells (EC). LysoPC decreased the release of EDNO caused by 5-HT, but did not affect the response to BK or mastoparan. LysoPC did not increase production of superoxide radicals detected by lucigenin-enhanced chemiluminescence. Western blot analysis showed no difference in the level of immunoreactive Gi alpha-2 between control and lysoPC-treated cells. Activation of the Gi-2 protein by serotonergic or alpha 2-adrenoceptor stimulation decreased the pertussis toxin-catalyzed ADP-ribosylation of Gi alpha-2 protein in membranes from control but not lysoPC-treated cells. However, direct activation of the Gi-2 protein by mastoparan inhibited the ADP-ribosylation in membranes from control and lysoPC-treated cells. The toxin-catalyzed reaction was reduced in lysoPC-treated cells or lysoPC-treated membranes. LysoPC reduced the ability of endothelin to increase GTP gamma S binding to the Gi-2 protein but did not affect the activity of mastoparan. These results suggest that lysoPC inhibits a pertussis toxin-sensitive signaling pathway in EC by an effect consistent with receptor:Gi-2-protein uncoupling.

Summary Intermittent intravenous methotrexate has been used to treat patients with locally advanced or metastatic transitional cell carcinoma of the bladder (40 cases) and of the renal pelvis (2 cases). Objective evidence of tumour regression, attributable to the methotrexate therapy, was observed in 11 patients (26 %) for 2 to 20 months. Several other patients gained relief of symptoms but in these there was no clear evidence of tumour regression. Toxic side‐effects from methotrexate interrupted treatment for a time in 29 patients but were seldom serious and were never fatal. It is concluded that intravenous methotrexate therapy is of value in the management of advanced bladder cancer. The possibility of improving tumour response and decreasing drug toxicity is discussed.