The effects of acute hypoxia on tissue oxygenation and circulating alarmins in healthy adults.

The binding of high-mobility group box-1 (HMGB-1) to the membrane receptor for advanced glycation end-products (mRAGE) is a key early mediator of non-infectious inflammation and its triggers include ischaemia/hypoxia. The effects of acute hypoxia on soluble RAGE (sRAGE) are unknown. Fourteen healthy adults (50 % women; 26.6+/-3.8 years) were assessed at baseline normoxia (T0), followed by four time-points (T90, 95, 100 and 180 min) over three hours of continuous normobaric hypoxia (NH, 4,450 m equivalent) and again 60 min after return to normoxia (T240). A 5-min exercise step test was performed during NH at T90. Plasma concentrations of HMGB-1, sRAGE VCAM-1, ICAM-1, VEGF IL-8 and IL-13 were measured using venous blood. Arterial and tissue oxygen saturations were measured using pulse oximetry (SpO(2)) and near-infrared spectroscopy (StO(2)), respectively. NH led to a significant reduction in SpO(2), StO(2), sRAGE and VEGF, which was compounded by exercise, before increasing to baseline values with normoxic restoration (T240). NH-exercise led to a paired increase in HMGB-1. sRAGE inversely correlated with HMGB-1 (r=-0.32; p=0.006), heart rate (r=-0.43; p=0.004) but was not linked to SpO(2) or StO(2). In conclusion, short-term NH leads to a fall in sRAGE and VEGF concentrations with a transient rise post NH-exercise in HMGB-1.

Uk Armed Forces unintentional firearm injuries.

OBJECTIVES: To report on the incidence of unintentional firearm discharge and injury across the UK Armed Forces and present several cases of this wounding phenomenon. METHOD: Munitions Incidents and Defects (MID) Cell data on UK Military Negligent Discharges and unintentional firearm injuries from 01 Jan 03 to 31 Dec 07 was categorised according to cause of injury, wound, service affiliation, incident context and weapon type. The injuries of three patients are described. RESULTS: Over the 5 year period there were 1158 Unintentional firearm discharges, forty three (4%) of which resulted in injury. Fifty five military personnel sustained unintentional firearm injuries during the review period, more than half of which were gunshot wounds and this included one fatality. The Regular Army suffers an average of 7.7 unintentional firearm injuries per 100 000 Regular Army person years. CONCLUSION: Unintentional firearm injury is well recognised across the civilian and police sectors worldwide. Despite the recent tempo of high grade training and operations that currently engage UK Armed Forces this form of injury remains uncommon. We hope to facilitate discussion with the chain of command to manage the risk of these injuries.