OBJECTIVE -To assess microcirculatory impairment and alterations of the skin oxygen supply in diabetic patients with foot at risk.RESEARCH DESIGN AND METHODS -This study evaluated skin blood flow in 21 type 2 diabetic patients with a foot at risk (defined as a foot with neuropathy but without ulceration or previous ulcerations), 20 type 2 diabetic patients without foot lesions or neuropathy, and 21 normal subjects as a control group. The skin blood flow was determined by measuring the transcutaneous oxygen pressure (TcPO 2 ) at the dorsum of the foot in supine and sitting position. The clinical assessment included standard measures of peripheral and autonomic neuropathy, but peripheral vascular disease was excluded by Doppler ultrasound.RESULTS -In supine position, TcPO 2 was significantly reduced (means Ϯ SE) in diabetic patients with foot at risk (6.04 Ϯ 0.52 kPa) compared with diabetic (7.14 Ϯ 0.43 kPa, P ϭ 0.035) and nondiabetic (8.10 Ϯ 0.44 kPa, P ϭ 0.01) control subjects. The sitting/supine TcPO 2 difference was higher in diabetic subjects with foot at risk (3.13 Ϯ 0.27 kPa) compared with both diabetic (2.00 Ϯ 0.18, P ϭ 0.004) and nondiabetic (1.77 Ϯ 0.15 kPa, P ϭ 0.0003) control subjects. The mean sitting/supine ratio was 1.70 Ϯ 0.12 in diabetic patients with foot at risk, 1.32 Ϯ 0.04 in diabetic control subjects, and 1.25 Ϯ 0.03 in nondiabetic control subjects (P ϭ 0.007). The sitting/supine TcPO 2 ratio was negatively correlated with the heart rate variation coefficient at rest (r ϭ Ϫ0.32, P ϭ 0.044) and at deep respiration (r ϭ Ϫ0.31, P ϭ 0.046).CONCLUSIONS -Our data indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot at risk. This is probably due to an impaired neurogenic blood flow regulation and may contribute to capillary hypertension, followed by disturbed endothelial function leading to edema and skin damage of the foot. The determination of TcPO 2 appears to be a useful tool in screening type 2 diabetic patients for foot at risk. Diabetes Care 24:1810 -1814, 2001F oot ulcerations in diabetic patients are a major health problem, often leading to lower-limb amputations and an increased death rate (1,2). The management of diabetic foot ulcers creates considerable costs, estimated at about $1.5 billion in the U.S. Medicare system in 1995 (3). Diabetic neuropathy, mechanical stress, and blood flow alterations are involved in the pathogenesis of diabetic foot ulceration (4,5). These factors interact with the microcirculation, resulting in the failure of skin capillary blood flow (5-9). Besides other factors, reduced skin oxygenation and both sensory and autonomic neuropathy increase the risk of foot ulceration, and screening for and detection of these factors may be useful (5,10). The autonomic nervous system, which supplies sympathetic adrenergic fibers to the arterioles and arteriovenous shunts, directly influences peripheral circulation (8,11). As shown in several studies, transcutaneous oxygen pressure (TcPO 2 ) measurement provides useful information about microcircu...

Although infectious agents such as Staphylococcus aureus have been implicated in the pathogenesis of Wegener's granulomatosis, the role of bacterial infections in the pathogenesis of other types of small-vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) is less clear. We describe a patient who developed a non-granulomatous necrotising small vessel vasculitis and perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO) after recurrent episodes of bacterial endocarditis due to Staph. aureus. Although cytoplasmic ANCA (c-ANCA) directed against proteinase 3 have been reported in single patients with bacterial endocarditis, to our knowledge this patient is the first reported case of an anti-MPO-ANCA positive systemic vasculitis following bacterial endocarditis.

The results indicated that the angiogenic molecules VEGF, FN, and TNF-alpha stimulate MMP-2 and -9 secretion from RPE and thus further promote CNV.