Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease

Clinical outcomes and quality of life 5 years after a randomized trial of concomitant or sequential phlebectomy following endovenous laser ablation for varicose veins

BackgroundEndovenous laser ablation (EVLA) is a popular treatment for superficial venous insufficiency. Debate continues regarding the optimal management of symptomatic varicose tributaries following ablation of the main saphenous trunk. This randomized trial compared the 5-year outcomes of endovenous laser therapy with ambulatory phlebectomy (EVLTAP) with concomitant ambulatory phlebectomy, and EVLA alone with sequential treatment if required following a delay of at least 6 weeks.MethodsPatients undergoing EVLA for great saphenous vein insufficiency were randomized to receive EVLTAP or EVLA alone with sequential phlebectomy, if required. Outcomes included disease-specific quality of life (QoL) (Aberdeen Varicose Vein Questionnaire; AVVQ), requirement for secondary procedures, clinical severity (Venous Clinical Severity Score; VCSS), residual and recurrent varicose tributaries, and generic QoL. Patients were followed up for 5 years.ResultsFifty patients were randomized equally into two parallel groups. The EVLTAP group had lower VCSS scores at 12 weeks (median 0 (i.q.r. 0-1) versus 2 (0-2); P <0·001), and lower AVVQ scores at 6 weeks (median 7·9 (i.q.r. 4·1-10·7) versus 13·5 (10·9-18·1); P < 0·001) and 12 weeks (2·0 (0·4-7·7) versus 9·6 (2·2-13·8); P = 0·015). VCSS and AVVQ scores were equivalent by 1 year, but only after 16 of 24 patients in the EVLA group, compared with one of 25 in the EVLTAP group (P < 0·001), had received a secondary intervention. From 1 to 5 years both groups had equivalent outcomes.ConclusionEVLA with either concomitant or sequential management of tributaries is acceptable treatment for symptomatic varicose veins, with both treatments achieving excellent results at 5 years. Concomitant treatment of varicosities is associated with optimal improvement in both clinical disease severity and QoL

Systematic review of compression following treatment for varicose veins

Background Consensus regarding compression following treatment of varicose veins has yet to be reached. This systematic review aims to establish the optimal compression regimen after venous treatment. Methods A systematic review of MEDLINE, Embase and CENTRAL was performed to identify randomized clinical trials (RCTs) investigating different compression strategies following treatment for superficial venous insufficiency. Results Seven RCTs comparing different durations and methods of compression fulfilled the inclusion criteria. The treatment modality was open surgery in three trials, foam sclerotherapy in two and endovenous laser ablation (EVLA) in two trials. The quality of the studies was variable, and significant sources of potential bias were present. Both the studies and compression regimens used were heterogeneous. Ten products were used in six general regimens for a duration of 0-42 days. One study suggested that 7 days rather than 2 days of stockings following EVLA was associated with superior quality of life and less pain at 1 week. Another study reported that, following surgery, application of a compression stocking after 3 days of bandaging was associated with a slightly longer recovery than no compression after 3 days. One study recorded compliance clearly, finding it to be only 40 per cent. The quality and heterogeneity of the studies precluded meta-analysis. Conclusion There is currently little quality evidence upon which to base any recommendations concerning compression following treatment for varicose veins. No recommendations possibl