Prevalence of leg ulceration in a London population.

BACKGROUND: Current prevalence estimates of chronic leg ulceration are frequently based on studies from the 1980s. During the last decade, major changes have occurred in the application of evidence-based practice to this condition. AIM: To determine the prevalence and cause of leg ulceration in a defined geographical population after 8 years of providing standardized evidence based protocols of care. DESIGN: Prospective survey. METHODS: Patients with leg ulceration of >4 weeks duration) within an integrated acute and community leg ulcer service were ascertained, interviewed and clinically assessed, using a standardized questionnaire on medical history, ulcer details and non-invasive vascular investigation to describe causes. Ulcers were classified by aetiology. RESULTS: We identified 113 patients in a population of 252 000, giving a crude prevalence of 0.45/1000 (95%CI 0.37-0.54/1000): 0.34/1000 in men, 0.54/1000 in women. Rates were highly dependent on age, increasing to 8.29 (men) and 8.06/1000 (women) in those aged >85 years. Of the responders, 62/113 (55%) had their ulcer for >1 year. Uncomplicated venous ulceration was observed in only 59/138 (43%) ulcerated limbs; a further 21 had ulceration primarily due to arterial disease. Complex causes were present in 48 (35%) limbs, mostly venous disease in combination with diabetes (35%), lymphoedema (42%) and rheumatoid arthritis (26%). DISCUSSION: Our prevalence of chronic leg ulceration is approximately one-third of that predicted by previous studies using similar methodologies in the 1980s. Patients with ulceration have more complex aetiologies than previously recognized, which may be a consequence of both increasing ulcer chronicity and age.

Iron Deficiency Developing in Patients with Homozygous Hypercholesterolaemia on Long-term Plasmapheresis is Significantly Contributed to by Extracorporeal Haemolysis.

Patients with homozygous hypeicholesterolaemia are notoriously refractory to pharmacologic intervention, leaving regular long-term plasmapheresis as one of the most effective forms of therapy. In this situation we noted the universal development of anaemia; accordingly, its pathogenesis was investigated in a stable cohort of patients over a two year period. Radionuclide studies were carried out in 8 of the 9 available individuals: of these 3 who were not on treatment and 3 out of 5 on the apheresis programme had mean red cell lifespan below the lower level of our normal range. The creation of an arterio-venous fistula and subsequent performance of plasma exchange procedures every two weeks was followed by a falling haemoglobin concentration and the appearance of hypochromasia and microcytosis. The latter was the result of substantial loss of iron through venesection, in the discard plasma and by a transient peak of the iron in the urine: the last two compartments were studied using inductively coupled plasma atomic emission spectrometry (ICP-AES). Such depletion could not be compensated for by a dietary intake of iron that barely met the recommended daily allowance whereas the anaemia reversed readily on oral supplementation. This is the first report of extracorporeal haemolysis in this clinical setting and recognition of its pathophysiology directly influences management. Thus, oral iron supplementation should prevent anaemia and its symptoms whilst also circumventing the paradoxical hyperviscosity that might otherwise occur from iron deficiency.

Location and size of carotid body-like organs (paraganglia) revealed in rats by the permeability of blood vessels to Evans blue dye.

We determined the number, distribution size, and morphology of paraganglia near the glossopharyngeal, vagus, and sympathetic nerves of rats. The location of paraganglia was revealed by a method that takes advantage of the comparatively high permeability of their blood vessels to Evans blue dye. Rats were fixed by vascular perfusion of glutaraldehyde 2 min after receiving an intravenous injection of Evans blue dye. Paraganglia appeared as circumscribed, intensely blue structures that were readily distinguished from unstained nerves associated with them. Similarly, some groups of small intensely fluorescent (SIF) cells in autonomic and sensory ganglia were surrounded by Evans blue at a time that other portions of the ganglia contained little detectable dye. An average of 92.5 (range 41-134) paraganglia and 41 (range 17-68) blue spots in ganglia were found in the neck, thorax and abdomen of each of 10 rats. Carotid bodies had a mean length of 601 +/- 123 micrometer, width of 275 +/- 65 micrometer, and volume of 25.1 +/- 11.2 micrometer 3 X 10(6). Other paraganglia had an average length of 168 +/- 108 micrometer, width of 77 +/- 41 micrometer, and volume of 0.87 +/- 1.55 micrometer 3 X 10(6). The total volume of paraganglion tissue averaged 128 micrometer 3 X 10(6) (range 62-215 micrometer 3 X 10(6)), 59% of which was due to paraganglia other than the carotid bodies. By using fluorescence microscopy, we verified that small catecholamine-containing cells, visible because of their yellow-green fluorescence induced by formaldehyde gas, were located in regions along nerves and within ganglia that contained extravascular dye, visible because of its red fluorescence. Electron-microscopic studies confirmed that blue-stained organs (presumptive paraganglia) associated with the superior laryngeal nerve and other branches of the vagus nerve contained cells morphologically similar to glomus cells of the carotid body. Celiac ganglia contained, in addition, some cells similar to chromaffin cells of the adrenal medulla. Paraganglia (but not in SIF cells in ganglia) were encapsulated by layers of perineurium, which may constitute a barrier to diffusion. Tortuous thin-walled blood vessels, some with a fenestrated endothelium, were present in all paraganglia examined and were near most groups of SIF cells in ganglia. Neural connections of the small catecholamine-containing cells varied. Most nerve terminals on cells in paraganglia resembled sensory nerve endings on glomus cells of the carotid body, although some were morphologically similar to preganglionic nerves on chromaffin cells of the adrenal medulla.