A Compression Kit of a Stocking and Three Superimposed Leggings Is Easy to Don and Dose Adjustable.

BACKGROUND: Forty percent of patients with chronic venous insufficiency (CVI) do not wear their indicated and prescribed compression stockings. Difficulties in donning and a feeling of constraint are the most common reasons for non-adherence. OBJECTIVE: The aim was to develop a compression stocking system that is easy to don and dose adjustable. METHODS: A modular compression stocking kit composed of an understocking and three superimposable leggings (SLLLs) was developed. Substocking pressures (P) at the thinnest part above the ankle (cB level) were 17 mm (understocking) + 15 + 10 + 10 mmHg (3 superimposed leggings; Hatra method). Twenty healthy subjects and 20 patients over 65 years with CVI donned the SLLL compression kit. P was measured in vivo (Picopress method) at the transition of the Achilles tendon to the calf muscle (level cB1) during rest and ankle movements (DSI; dynamic stiffness index) and compared with a strong compression stocking of 40 mmHg (S40). RESULTS: Twenty (20/20) patients aged over 65 with CVI (C4-6) successfully donned the SLLL compression kit without aid, compared with 12 (12/20) who were able to don the S40 without aid (p = .02). In vivo resting P at level cB1 was 34.3 mmHg (SLLL) compared with 37.3 mmHg (S40) (p = .1). The DSI was 16.1 (SLLL) compared with 17.9 (p = .79; S40; CVI group). CONCLUSION: The physical properties of the SLLL compression stocking kit correspond to the characteristics of a strong stocking at rest and exercise (DSI). The donning success rate is excellent (100%). A further potential advantage is that the SLLL leg compression kit is dose adjustable, according to indication or patient tolerance. Wearing comfort over periods of several days and clinical effectiveness need to be investigated in future trials.

Reversal of UVA skin photosensitivity and DNA damage in kidney transplant recipients by replacing azathioprine.

Azathioprine is associated with enhanced skin photosensitivity to ultraviolet A (UVA) and leads to incorporation of 6-thioguanine (6-TG) into DNA of dividing cells. Unlike canonical DNA, 6-TG DNA is damaged by UVA, which comprises more than 90% of the ultraviolet reaching earth. Skin photosensitivity to UVA and UVB was measured in 48 kidney transplant patients immunosuppressed either by azathioprine (n = 32) or mycophenolate (n = 16). In 23 patients, azathioprine was subsequently replaced by mycophenolate and skin photosensitivity, DNA 6-TG content in peripheral blood mononuclear cells, and susceptibility to UVA-induced DNA damage were monitored for up to 2 years. The mean minimal erythema dose to UVA on azathioprine was twofold lower than on mycophenolate. Three months after replacing azathioprine by mycophenolate mofetil, the minimal erythema dose to UVA had increased from 15 to 25 J/cm(2) (p < 0.001) accompanied by reduced DNA 6-TG content. P53 protein expression in irradiated skin indicated reduced susceptibility to UVA-induced DNA damage. 6-TG DNA in peripheral blood mononuclear cells remained measurable for over 2 years. Replacing azathioprine selectively reduced the skin photosensitivity to UVA, attenuated UVA-induced skin DNA damage, and is likely based on incorporated 6-TG in DNA.

A chemically modified antibody mediates complete eradication of tumours by selective disruption of tumour blood vessels.

BACKGROUND: The possibility of eradicating cancer by selective destruction of tumour blood vessels may represent an attractive therapeutic avenue, but most pharmaceutical agents investigated so far did not achieve complete cures and are not completely specific. Antibody conjugates now allow us to evaluate the impact of selective vascular shutdown on tumour viability and to study mechanisms of action. METHODS: We synthesised a novel porphyrin-based photosensitiser suitable for conjugation to antibodies and assessed anticancer properties of its conjugate with L19, a clinical-stage human monoclonal antibody specific to the alternatively spliced EDB domain of fibronectin, a marker of tumour angiogenesis. RESULTS: Here we show in two mouse model of cancer (F9 and A431) that L19 is capable of highly selective in vivo localisation around tumour blood vessels and that its conjugate with a photosensitiser allows selective disruption of tumour vasculature upon irradiation, leading to complete and long-lasting cancer eradication. Furthermore, depletion experiments revealed that natural killer cells are essential for the induction of long-lasting complete responses. CONCLUSIONS: These results reinforce the concept that vascular shutdown can induce a curative avalanche of tumour cell death. Immuno-photodynamic therapy may be particularly indicated for squamous cell carcinoma of the skin, which we show to be strongly positive for markers of angiogenesis.