BackgroundCVD in obesity and T2DM are associated with endothelial activation, elevated plasma vascular inflammation markers and a prothrombotic state. We examined the contribution of FFA to these abnormalities following a 48-hour physiological increase in plasma FFA to levels of obesity and diabetes in a group of healthy subjects.Methods40 non-diabetic subjects (age = 38 ± 3 yr, BMI = 28 ± 1 kg/m2, FPG = 95 ± 1 mg/dl, HbA1c = 5.3 ± 0.1%) were admitted twice and received a 48-hour infusion of normal saline or low-dose lipid. Plasma was drawn for intracellular (ICAM-1) and vascular (VCAM-1) adhesion molecules-1, E-selectin (sE-S), myeloperoxidase (MPO) and total plasminogen inhibitor-1 (tPAI-1). Insulin sensitivity was measured by a hyperglycemic clamp (M/I).ResultsLipid infusion increased plasma FFA to levels observed in obesity and T2DM and reduced insulin sensitivity by 27% (p = 0.01). Elevated plasma FFA increased plasma markers of endothelial activation ICAM-1 (138 ± 10 vs. 186 ± 25 ng/ml), VCAM-1 (1066 ± 67 vs. 1204 ± 65 ng/ml) and sE-S (20 ± 1 vs. 24 ± 1 ng/ml) between 13-35% and by ≥ 2-fold plasma levels of myeloperoxidase (7.5 ± 0.9 to 15 ± 25 ng/ml), an inflammatory marker of future CVD, and tPAI-1 (9.7 ± 0.6 to 22.5 ± 1.5 ng/ml), an indicator of a prothrombotic state (all p ≤ 0.01). The FFA-induced increase was independent from the degree of adiposity, being of similar magnitude in lean, overweight and obese subjects.ConclusionsAn increase in plasma FFA within the physiological range observed in obesity and T2DM induces markers of endothelial activation, vascular inflammation and thrombosis in healthy subjects. This suggests that even transient (48-hour) and modest increases in plasma FFA may initiate early vascular abnormalities that promote atherosclerosis and CVD.
Little information is available about several important aspects of the treatment of melioidosis osteomyelitis and septic arthritis. We undertook a retrospective review of 50 patients with these conditions in an attempt to determine the effect of location of the disease, type of surgical intervention and duration of antibiotic treatment on outcome, particularly complications and relapse. We found that there was a 27.5% risk of osteomyelitis of the adjacent bone in patients with septic arthritis in the lower limb. Patients with septic arthritis and osteomyelitis of an adjacent bone were in hospital significantly longer (p = 0.001), needed more operations (p = 0.031) and had a significantly higher rate of complications and re-presentation (p = 0.048). More than half the patients (61%), most particularly those with multifocal bone and joint involvement, and those with septic arthritis and osteomyelitis of an adjacent bone who were treated operatively, needed more visits to theatre.
Extra-corporeal membrane oxygenation (ECMO) is a well-established treatment for cardiopulmonary failure. Based on the requirement for cardiac and or respiratory support different configurations of ECMO circuits are utilized. Vascular complication of ECMO constitutes the most important determinant of treatment outcomes. The complications are primarily related to limb ischemia, vascular injury, hemorrhage, and infection. Endovascular and surgical treatment options are the cornerstone for managing vascular complications of ECMO.
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