[Effectiveness of a micronized purified flavonoid fraction (MPFF) in the healing process of lower limb ulcers. An open multicentre study, controlled and randomized]. / Efficacia della frazione flavonoica purificata micronizzata (FFPM) nell'aumentare la guarigione della ulcere agli arti inferiori. Studio multicentrico in aperto, controllato e randomizato.

OBJECTIVE: To determine the increase in healing rate of venous ulcer in patients receiving a micronised purified flavonoid fraction (MPFF) as supplementation to standard local care. DESIGN: A randomised, open, controlled, multicentre study. SETTING: Departments of Dermatology and University Outpatients Clinics. PATIENTS: One hundred and forty patients with chronic venous insufficiency and venous ulcers. INTERVENTION: PATIENTS received standard compressive therapy plus external treatment alone or 2 tablets of MPFF daily in addition to the above treatment for 24 weeks. MAIN OUTCOME MEASURE: Healing of ulcers and their reduction in size after 24 weeks of treatment. RESULTS: The percentage of patients whose ulcers healed completely was found to be markedly higher in those receiving MPFF in addition to standard external and compressive treatment than in those treated with conventional therapy alone (46.5% vs 27.5%; p<0.05. OR=2.3, 95% CI 1.1-4.6). Ulcers with diameters <3 cm were cured in 71% of patients in the MPFF group and in 50% of patients in the control group, whereas ulcers between 3 and 6 cm in diameter were cured in 60% and 32% of patients (p<0.05), respectively. The mean reduction in ulcer size was also found to be greater in patients treated with MPFF (80%) than in the control group (65%) (p<0.05). The cost-effectiveness ratio (cost per healed ulcer) in the MPFF group was 1026.2 compared with 1871.8 in the control group. CONCLUSIONS: These results indicate that MPFF significantly improves the cure rate in patients with chronic venous insufficiency.

The pattern and level of cytokines secreted by Th1 and Th2 lymphocytes of syphilitic patients correlate to the progression of the disease.

The results of our previous work indicated that cell-mediated immune response, of importance in protection against Treponema pallidum, is distinctly inhibited at certain periods of syphilitic infection. Considering that cytokines, produced by Th1 lymphocytes, take part in this response and that their secretion may be regulated by cytokines of Th2 lymphocytes, we examined if, and in which stages of syphilis, such a regulation may exist. In this study we have examined the ability of cells to produce IL-2, IFN and TNF (Th1 or Th1 like cytokines) as well as IL-6 and IL-10 (Th2 or Th2 like cytokines). It was found that cells of syphilitic patients were able to produce IL-2, IFN, TNF, IL-10 and weakly IL-6 already in primary seronegative syphilis. At the same stage of syphilis, but seropositive, ability of Th1 lymphocytes to produce cytokines reached the highest values, whereas the cells producing IL-10 lost this ability. The cells producing IL-6 and MIF had the highest ability in secondary early syphilis. In this stage of syphilis again slightly increased the ability of cells to secrete IL-10, which reached the highest value in early latent syphilis. The growing ability to produce IL-6 and IL-10 was accompanied with a diminished production of IL-2, IFN and TNF nearly in all stages of syphilis. Only MIF, in contrast to other cytokines, was produced in late syphilis without distinct changes. The greatest suppression of Th1 lymphocytes to produce cytokines and cells to secretion of MIF was found in early latent syphilis when the level of IL-10 in cell culture supernates was the highest. High ability of Th2 lymphocytes to cytokines secretion in late syphilis and low ability of Th1 ones, which are very important for cell-mediated immune response, may be the reason for facilitating T. pallidum multiplication and development of latent stages of disease despite presence of immunologically competent cells.

The effect of topical 0.75% metronidazole gel on malodorous cutaneous ulcers.

The unpleasant smell of infected fungating tumors and benign cutaneous ulcers is a distressing clinical problem, known to be associated with anaerobic infection. Topical metronidazole 0.8% gel has been shown to decrease smell from fungating malodorous tumors. This study was conducted to assess prospectively the subjective and bacteriological response to 0.75% metronidazole gel to decrease smell from these lesions and to assess whether bacterial contamination of the tubes of gel occurs during use. Forty-seven patients with benign or malignant cutaneous lesions associated with a foul smell were assessed for smell, pain, appearance, and bacteriological profile before entry and at 7 and 14 days. Forty-one (95%) of the 43 patients assessed at 14 days reported decreased smell. Anaerobic infection was initially found in 25 (53%) of patients and was eliminated in 21 (84%) of these. At review after 7 days, patients reported less pain from the lesions. Discharge and associated cellulitis were also observed to decrease significantly.

The ability of peripheral blood mononuclear cells (PBMC) of syphilitic patients to produce IL-2.

The cell-mediated immune response of importance in protection against Treponema pallidum, is distinctly suppressed in some stages of the disease. This may be a result of decreased ability of cells to produce IL-2, or IL-2 absorption by different factors. The experiments were designed to evaluate the ability of peripheral blood mononuclear cells (PBMC) of patients with different stages of syphilis to produce IL-2, and to investigate the causes which could possibly limit its activity. The ability of the PBMC of syphilitic patients to produce IL-2 develops at the beginning of the disease, reaching a maximum in primary seropositive syphilis. In the next stages of the disease this capability is distinctly lowered. The lowest was in malignant syphilis and tabes dorsalis, i.e. during severe disease. Absorption of adherent cells from PBMC increased the ability of lymphocytes to produce IL-2. The highest level of this interleukin was observed at the stages of the disease where suppression was the deepest. Sera of both control and syphilitic patients contained IL-2 inhibitor. Its level was the highest in early and late latent syphilis where no symptoms of disease were present. In all syphilitic sera a distinctly elevated level of soluble IL-2 receptors (sIL-2R) was also found. Its high level was noted in sera of patients in which PBMC had the weakest ability to produce IL-2. These findings suggest that sIL-2R may be bound to IL-2 and in this way would lead to weakening of T cell function and of resistance against Treponema pallidum infection.

Comparison of two dressings in the treatment of venous leg ulcers.

A report of a clinical trial that evaluated the efficacy of a polyurethane foam dressing and a hydrocolloid dressing applied beneath a compression bandage.

The occurrence of IgA pemphigus foliaceus without neutrophilic infiltration.

A 70-year-old woman with pemphigus foliaceus is reported. Direct immunofluorescence performed on perilesional skin revealed deposits of IgA, C3 and lambda chains in the intercellular substance of the upper stratum spinosum. Indirect immunofluorescence demonstrated serum antibodies of the IgA class against the intercellular region of the upper epidermis at an initial titre of 1:2560. Histological studies, performed together with immunofluorescence, revealed an absence of a distinct neutrophil infiltrate either in the epidermis or dermis, contrary to the findings in cases with intra-epidermal IgA deposits reported previously.

The ability of peripheral blood mononuclear cells of rabbits infected with Treponema pallidum to produce IL-2.

It was previously found that the cell-mediated immune response involved in protection against Treponema pallidum is distinctly suppressed during some periods in the course of syphilis infection in rabbits. This may be a result of the weak ability of cells to produce Interleukin-2 (IL-2) as well as of IL-2 absorption. The ability of peripheral blood mononuclear cells (PBMC) of syphilitic rabbits to produce IL-2 develops within the first two weeks after infection reaching a maximum in about the eleventh week. In infection of longer duration, this capability was distinctly lowered. This low level of activity (no higher than in PBMC of normal rabbits) was maintained for 31 weeks. The ability of PBMC to absorb IL-2, in parallel with its production, was found at the same time in the course of syphilis infection (7-11 weeks). In long-lasting syphilis (more than 12 weeks) both abilities seem to be inhibited. Sera of syphilitic rabbits were found to have a higher level of IL-2 inhibitor than those of normal rabbits. Only in syphilis lasting 9 to 11 weeks, when the production of IL-2 was the greatest, was the level of IL-2 inhibitor nearly the same as in normal rabbit sera. In syphilis lasting longer, the increased level of inhibitor was accompanied by a decreased ability of cells to produce IL-2. These findings suggest that IL-2 inhibitor may be bound to IL-2 or IL-2 receptor on T lymphocytes and in this way would lead to weakening of T cell function and resistance against Treponema pallidum infection.