No benefit could be found using additional TA to reduce the vein diameter before the treatment.

WHAT THIS PAPER ADDS Currently, investigations on patients with superficial venous insufficiency are limited invariably to assessing the presence and sites of reflux. This approach is satisfactory for most patients and directs the location of treatment. However, symptoms and signs do not always improve, may not be related to clinical severity, and recurrence is common. For this reason and as in most other chronic diseases, it may be advantageous to have an objective reference standard to quantify the drainage insufficiency and then to measure its response to treatment and follow up. This study investigates four such measurement parameters and their relationships with each other.Objectives: Reflux assessment with ultrasound (U/S) is usually qualitative. Quantitative measurements of superficial venous insufficiency (SVI) include the venous arterial flow index (VAFI), recirculation index (RCI), venous filling index (VFI), and the postural diameter change (PDC) of the saphenous trunk. The aim was to investigate their relationship. Materials and methods: This was an observational study performed on patients with varicose veins and hospital employees. Four haemodynamic parameters were measured in 21 legs from 16 subjects. Legs were divided into no reflux (n ¼ 7) and reflux (n ¼ 14). The VAFI is the U/S ratio of common femoral vein volume flow divided by the common femoral artery volume flow, performed supine. The RCI is the U/S ratio of reflux volume over antegrade volume within the saphenous trunk after calf compression, standing. The VFI is the rate of calf volume increase on dependency measured in mL/s, using air plethysmography. The PDC is the percentage reduction of the saphenous trunk diameter from standing to lying, using U/S. Results: The clinical part of the CEAP classification was:All four tests demonstrated significant differences between the two groups with minimal overlap (Mann Whitney U test): VAFI (p ¼ .028), RCI (p < .0005), VFI (p ¼ .001), and PDC (p ¼ .014). Furthermore, significant correlations were observed with the tests: VAFI vs. RCI (r ¼ .532, p ¼ .015), VFI (r ¼ .489, p ¼ .025) and PDC (r ¼ À.474, p ¼ .030); RCI vs. VFI (r ¼ .446, p ¼ .043) and PDC (r ¼ À.527, p ¼ .014). Conclusions: Superficial venous drainage insufficiency should not be confined to an U/S assessment of the presence of reflux, which is qualitative. Quantitative data may be provided using the VAFI, RCI, VFI, and PDC. Understanding why there are significant correlations among these parameters and the preferred objective reference test requires further work.

There is a significant correlation between the VAFI measured using sonography and MRI. The study confirmed the elevation of VAFI in patients with chronic venous disease.

Despite numerous encouraging reports in the literature, the efficiency of cell penetrating peptides (CPPs) in promoting cellular delivery of bioactive cargos is still limited. To extend our current understanding of the underlying limitations of such approaches, we performed quantitative uptake studies of different chemically modified (2'-O-methyl, LNA and PNA) steric block oligonucleotides, targeted against a mutated splice site inserted in a firefly luciferase reporter gene construct, applying the peptide carrier MPGalpha as a model system. The peptide formed stable noncovalent complexes with phosphorothioate oligonucleotide (PTO) and locked nucleic acid (LNA) modified oligonucleotides, whereas the neutral peptide nucleic acid (PNA) had to be hybridized to an unmodified DNA to allow for complex formation. Detailed quantitative uptake studies revealed comparable numbers of intracellular PTO and LNA oligonucleotides after peptide-mediated delivery. Surprisingly, the PTO derivative showed the strongest upregulation of reporter gene activity of about 100-fold followed by the PNA (40-fold) and LNA (10-fold). Electroporation and microinjection studies proved that delivery itself was not the limiting factor for the low activity of the LNA derivative. Maximal achievable reporter gene activity could be observed only after addition of chloroquine (CQ), indicative of an endosomal pathway involved. This is in line with nuclear microinjection experiments, which show that the minimal number of steric block molecules needed to trigger the observed reporter upregulation is about two orders of magnitude lower than determined after peptide or cationic lipid delivery.

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