S. G. K. Packer

Chelation therapy for intermittent claudication. A double-blind, randomized, controlled trial.

BackgroundThe use of repeated intravenous infusions of EDTA, which has become known as “chelation therapy,” has been promoted for treating intermittent claudication as well as a wide range of other disorders. Multiple reports of excellent results in large numbers of patients have encouraged the use of this regimen. The lack of well-controlled studies substantiating the benefits of this treatment has limited its use mainly to private clinics. The aim of the study was to assess the benefits of chelation therapy in patients with intermittent claudication. Methods and ResultsA double-blind, randomized, controlled trial included 32 patients with intermittent claudication who were randomized to a treatment group (15) and a control group (17). Main outcome measures were subjective and measured walking distances and ankle/brachial pulse indices. Other outcome measures included lifestyle and subjective parameters of improvement, cardiac function, ECG, renal function, hematology, blood glucose, and lipid biochemistry. No clinically significant differences in main outcome measures between chelation therapy and placebo groups were detected up to 3 months after treatment. Measures of mood state, activities of daily living, and quality of life factors were not consistently affected by chelation therapy. An equal propor-tion (13%) of each group thought that they had received the active agent. The proportion of patients showing an improvement in walking distance was not significantly different between the chelation group (60%) and the control group (59%). ConclusionsChelation therapy has no significant beneficial effects over placebo in patients with intermittent claudication.

The alternative lengthening of telomeres pathway may operate in non-neoplastic human cells†

The alternative lengthening of telomeres (ALT) mechanism represents an alternative to the enzyme telomerase in the maintenance of mammalian telomeres in 25–60% of sarcomas and a minority of carcinomas (about 5–15%). ALT‐positive cells are distinguished by long and heterogeneous telomere length distributions by terminal restriction fragment (TRF) Southern blotting. Another diagnostic marker of ALT is discrete nuclear co‐localized signals of telomeric DNA and the promyelocytic leukaemia protein (PML), referred to as ALT‐associated PML bodies (APBs). Recently, we detected smaller sized co‐localized PML and telomere DNA (APB‐like) bodies in endothelial cells adjacent to astrocytoma tumour cells in situ. In this study, we examined a wide variety of non‐neoplastic tissues, and report that co‐localized signals of PML and telomere DNA are present in endothelial, stromal, and some epithelial cells. Co‐localized signals of PML and telomere DNA showed an increased frequency in non‐neoplastic cells with DNA damage. These results suggest that a mechanism similar to that in ALT‐positive tumours also operates in non‐neoplastic cells, which may be activated by DNA damage. Copyright

Preservation of Skin Vasoconstrictor Responses in Chronic Atherosclerotic Peripheral Vascular Disease

Peripheral neuropathy is often found in ischemic limbs with nondiabetic atherosclerotic peripheral vascular disease (PVD). Sensory symptoms such as burning pain are common in severely ischemic limbs, and sympathectomy has been undertaken for ischemic rest pain. The authors assessed noninvasive quantitative skin vasomotor reflexes in toes and standard systemic cardiovascular autonomic tests in 44 PVD subjects with varying severity of limb ischemia, 30 age-matched control subjects, and nine PVD subjects associated with diabetes. Skin vasoconstrictor reflexes to inspiratory gasp, Valsalva maneuver, and postural change, and the postischemic reactive hyperemic response, were evaluated by the measurement of skin blood flow on toe pads by use of a laser Doppler flowmeter. Vasoconstrictor responses were not significantly different between PVD toes, even in severely ischemic limb, and age-matched controls. Reactive hyperemia was significantly less in PVD than in controls. Cardiovagal and systemic vasoconstrictor reflexes were also evaluated. All PVD subjects showed normal systemic cardiovascular reflexes. In contrast, these reflexes were severely impaired in diabetic PVD. The authors demonstrated that skin vasoconstrictive sympathetic reflex is preserved in chronically ischemic limbs with PVD, suggesting that sympathetic nerve fibers are relatively resistant to chronic ischemia.

Acute bilateral renal artery occlusion: successful revascularization with streptokinase

A case of acute oliguric renal failure due to bilateral renal artery occlusion is described. The renal function was restored to normal 36 h after the embolic event by revascularization with streptokinase.