ICS often presents as sudden unilateral left lower extremity pain and swelling in young to middle-aged female patients after pregnancy, surgery, or a period of inactivity. Venography, intravascular ultrasound, and magnetic resonance venography demonstrate high sensitivity, whereas APG-outflow fraction demonstrates low sensitivity in the diagnosis of ICS. Endovascular stenting and angioplasty provide safe and effective early and intermediate-term treatment of symptomatic ICS.
Few studies have documented relationships between endovascular therapy, duplex ultrasonography (DUS), post-thrombotic syndrome (PTS), and quality of life (QOL). The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial randomized 692 patients with acute proximal deep vein thrombosis (DVT) to receive anticoagulation or anticoagulation plus pharmacomechanical catheter-directed thrombolysis (PCDT). Compression DUS was obtained at baseline, 1 month and 12 months. Reflux DUS was obtained at 12 months in a subset of 126 patients. Clinical outcomes were collected over 24 months. At 1 month, patients who received PCDT had less residual thrombus compared to Control patients, evidenced by non-compressible common femoral vein (CFV) (21% vs 35%, p < 0.0001), femoral vein (51% vs 70%, p < 0.0001), and popliteal vein (61% vs 74%, p < 0.0001). At 12 months, in the ultrasound substudy, valvular reflux prevalence was similar between groups (85% vs 91%, p = 0.35). CFV non-compressibility at 1 month was associated with higher rates of any PTS (61% vs 46%, p < 0.001), a higher incidence of moderate-or-severe PTS (30% vs 19%, p = 0.003), and worse QOL (difference 8.2 VEINES-QOL (VEnous INsufficiency Epidemiological and Economic Study on Quality of Life) points; p = 0.004) at 24 months. Valvular reflux at 12 months was associated with moderate-or-severe PTS at 24 months (30% vs 0%, p = 0.01). In summary, PCDT results in less residual thrombus but does not reduce venous valvular reflux. CFV non-compressibility at 1 month is associated with more PTS, more severe PTS, and worse QOL at 24 months. Valvular reflux may predispose to moderate-or-severe PTS. ClinicalTrials.gov Identifier NCT00790335.
The hypothesis that dihydrolipoamide dehydrogenases (E3s) have tertiary structures very similar to that of human glutathione reductase (GR) was tested in detail by three separate criteria: (1) by analyzing each putative secondary structural element for conservation of appropriate polar/nonpolar regions, (2) by detailed comparison of putative active site residues in E3s with their authentic counterparts in human GR, and (3) by comparison of residues at the putative dimeric interface of the E3s with the authentic residues in GR. All three criteria are satisfied in a convincing way for the 7 E3s that were considered, supporting the conclusion that the structural scaffolding and the overall tertiary structure (which determines the location of functional sites and residues) are remarkably similar for the E3s and for GR. These analyses together with the crystal structures of human erythrocyte GR formed the basis for construction of a molecular model for human E3. The cofactor FAD and the substrates NAD and lipoic acid were also included in the model. Unexpectedly, the surface residues in the cleft that holds the lipoamide were found to be highly charged and predominantly acidic, allowing us to predict that the region around the lipoamide in the subunit should be basic in nature. The molecular model can be tested by site-directed mutagenesis of residues predicted to be in the dihydrolipoamide acetyltransferase subunit binding cleft.
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