Oxpentifylline treatment of venous ulcers of the leg.

OBJECTIVE--To determine the effect of oxpentifylline on the healing of venous ulcers of the leg. DESIGN--Double blind, randomised, prospective, placebo controlled, parallel group study. SETTING--Four outpatient clinics treating leg ulcers in England and the Republic of Ireland. PATIENTS--80 Consecutive patients with clinical evidence of venous ulceration of the leg in whom appreciable arterial disease was excluded by the ratio of ankle to brachial systolic pressure being greater than 0.8. INTERVENTIONS--All patients received either oxpentifylline 400 mg three times a day by mouth or a matching placebo for six months (or until their reference ulcer healed if this occurred sooner) in addition to a locally standardised method of compression bandaging. MAIN OUTCOME MEASURES--The primary end point was complete healing of the reference ulcer within six months. The secondary end point was the change in the area of the ulcer over the six month observation period. RESULTS--Complete healing of the reference ulcer occurred in 23 of the 38 patients treated with oxpentifylline and in 12 of the 42 patients treated with a placebo. Life table analysis showed that the proportion of ulcers healed at six months was 64% in the group treated with oxpentifylline compared with 34% in the group treated with a placebo (log rank test chi 2 = 4.78, p = 0.03), which was significant (odds ratio = 1.81, 95% confidence interval 1.20 to 2.71). CONCLUSION--Oxpentifylline used in conjunction with compression bandaging improves the healing of venous ulcers of the leg.     

A systematic review of compression treatment for venous leg ulcers.

OBJECTIVE: To estimate the clinical and cost effectiveness of compression systems for treating venous leg ulcers. METHODS: Systematic review of research. Search of 19 electronic databases including Medline, CINAHL, and Embase. Relevant journals and conference proceedings were hand searched and experts were consulted. MAIN OUTCOME MEASURES: Rate of healing and proportion of ulcers healed within a time period. STUDY SELECTION: Randomised controlled trials, published or unpublished, with no restriction on date or language, that evaluated compression as a treatment for venous leg ulcers. RESULTS: 24 randomised controlled trials were included in the review. The research evidence was quite weak: many trials had inadequate sample size and generally poor methodology. Compression seems to increase healing rates. Various high compression regimens are more effective than low compression. Few trials have compared the effectiveness of different high compression systems. CONCLUSIONS: Compression systems improve the healing of venous leg ulcers and should be used routinely in uncomplicated venous ulcers. Insufficient reliable evidence exists to indicate which system is the most effective. More good quality randomised controlled trials in association with economic evaluations are needed, to ascertain the most cost effective system for treating venous leg ulcers.     

Controlled trial of Iodosorb in chronic venous ulcers.

Cadexomer iodine (Iodosorb) is a hydrophilic starch powder containing iodine, which is a suitable dressing for granulating wounds such as venous ulcers. A total of 61 outpatients with chronic venous ulcers participated in a randomised optional crossover trial using cadexomer iodine or a standard dressing for their ulcers. The trial lasted for 24 weeks or until the ulcer had healed. Two patients withdrew during the course of the trial. Both treatments were highly effective, but the epithelium of ulcers dressed with cadexomer iodine grew again significantly faster (p less than 0.001). At the midpoint of the trial (12th week) 13 of 30 patients receiving standard treatment were changed to cadexomer iodine, while only three of 29 receiving cadexomer iodine changed to the standard dressing (p less than 0.02). In most cases ulcers were dressed and rebandaged daily by the patients themselves after instruction and supervision. This may be better than having dressings and bandages applied by professionals less regularly.     

Pathomechanism of chronic venous insufficiency and leg ulcer

Uniform view of chronic venous diseases has been formed in the last 3 decades. Chronic venous insufficiency (CVI) is a functional disorder of the venous system of the lower limb. The basis of the pathology is always the venous hypertension caused by valvular insufficiency and reflux with or without venous outflow obstruction. Epifascial, subfascial and transfascial forms of CVI can be distinguished. In the practice these forms are almost always combined. The consistent venous hypertension is the initiating factor in alterations in the microcirculation which leads to skin changes and venous ulceration. The precise mechanism of the development of venous leg ulcer is still uncertain. A recent hypothesis suggests that leukocytes are trapped in the capillaries and attaching to the endothel they become activated and release proteolytic enzymes, free radicals which have destructive effects on lipid membranes, proteins as well as on many connective tissue compounds. The endothelium plays active role in the complex mechanism. Increased expression of tissue metalloproteinases has been observed in the periulcer skin. The presence of perivascular leukocyte infiltration and fibrin cuff is a reflexion of an inflammatory process. The clinical stages of CVI are likely to be the results of a systemic inflammatory response to a period of venous hypertension.     

G20210A prothrombin gene mutation identified in patients with venous leg ulcers

The G20210A mutation variant of prothrombin gene is the second most frequent mutation identified in patients withdeep venous thrombosis, after factor V Leiden. The risk for developing deep venous thrombosis is high in patients identified as heterozygous for G20210A mutation. In order to identify this polymorphism in the gene coding prothrombin, the 345bp fragment in the 3'- untranslated region of the prothrombin gene was amplified using amplification by polymerase chain reaction and enzymatic digestion by HindIII (restriction endonuclease enzyme). The products of amplification and enzymatic's digestion were analized using agarose gel electrophoresis. We investigated 20 patients with venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of the patients in the control group had G20210A mutation. Our study confirms the presence of G20210A mutation in the Romanian population. Our study also shows the link between venous leg ulcers and this polymorphism in the prothrombin gene.     

Sustained compression and healing of chronic venous ulcers.

STUDY OBJECTIVE--Comparison of four layer bandage system with traditional adhesive plaster bandaging in terms of (a) compression achieved and (b) healing of venous ulcers. DESIGN--Part of larger randomised trial of five different dressings. SETTING--Outpatient venous ulcer clinic in university hospital. PATIENTS--(a) Pressure exerted by both bandage systems was measured in the same 20 patients. (b) Healing with the four layer bandage was assessed in 148 legs in 126 consecutive patients (mean age 71 (SE 2); range 30-96) with chronic venous ulcers that had resisted treatment with traditional bandaging for a mean of 27.2 (SE 8) months. INTERVENTIONS--(a) Four layer bandage system or traditional adhesive plaster bandaging for pressure studies; (b) four layer bandaging applied weekly for studies of healing. END POINTS--(a) Comparison of pressures achieved at the ankle for up to one week; (b) complete healing within 12 weeks. MEASUREMENTS AND MAIN RESULTS--(a) Four layer bandage produced higher initial pressures at the ankle of 42.5 (SE 1) mm Hg compared with 29.8 (1.8) for the adhesive plaster (p less than 0.001; 95% confidence interval 18.5 to 6.9). Pressure was maintained for one week with the four layer bandage but fell to 10.4 (3.5) mm Hg at 24 hours with adhesive plaster bandaging. (b) After weekly bandaging with the four layer bandage 110 of 48 venous ulcers had healed completely within 12 (mean 6.3 (0.4)) weeks. CONCLUSION--Sustained compression of over 40 mm Hg achieved with a multilayer bandage results in rapid healing of chronic venous ulcers that have failed to heal in many months of compression at lower pressures with more conventional bandages.     

Randomised,double blind placebo controlled trial of pentoxifylline in the treatment of venous leg ulcers

ObjectiveTo determine whether pentoxifylline 400 mg (Trental 400) taken orally three times daily, in addition to ambulatory compression bandages and dressings, improves the healing rate of pure venous ulcers.DesignRandomised, double blind placebo controlled trial, parallel group study of factorial design, permitting the simultaneous evaluation of alternative pharmaceutical, bandaging, and dressings materials.SettingLeg ulcer clinics of a teaching and a district general hospital in southern Scotland.Participants200 patients with confirmed venous ulcers and in whom other major causal factors were excluded.InterventionsPentoxifylline 400 mg three times daily or placebo.ResultsComplete healing occurred in 65 of the 101 (64%) patients receiving pentoxifylline and 52 of the 99 (53%) patients receiving placebo.ConclusionsThe difference in the healing rates between patients taking pentoxifylline and those taking placebo did not reach statistical significance.

Key messages

• Leg ulcers cost the NHS around £400 million per annum
• 50%-75% of venous leg ulcers can be succesfully treated with dressings and compression bandages but take many months to heal
• A drug that reduced the healing time of venous ulcers would be useful, although no agent has been proved to be effective to date
• Trials with pentoxifylline, a vasoactive drug used in the treatment of peripheral vascular diseases, as an adjunct to the treatment of venous ulcers have been inconclusive
• At the 5% level, pentoxifylline had a non-significant effect on healing rates of pure venous ulcers

     

Success rate of split-thickness skin grafting of chronic venous leg ulcers depends on the presence of Pseudomonas aeruginosa: a retrospective study

The last years of research have proposed that bacteria might be involved in and contribute to the lack of healing of chronic wounds. Especially it seems that Pseudomonas aeruginosa play a crucial role in the healing. At Copenhagen Wound Healing Centre it was for many years clinical suspected that once chronic venous leg ulcers were colonized (weeks or months preoperatively) by P. aeruginosa, the success rate of skin grafting deteriorated despite aggressive treatment. To investigate this, a retrospective study was performed on the clinical outcome of 82 consecutive patients with chronic venous leg ulcers on 91 extremities, from the 1^st of March 2005 until the 31^st of August 2006. This was achieved by analysing the microbiology, demographic data, smoking and drinking habits, diabetes, renal impairment, co-morbidities, approximated size and age of the wounds, immunosuppressive treatment and complicating factors on the clinical outcome of each patient. The results were evaluated using a Student T-test for continuous parameters, chi-square test for categorical parameters and a logistic regression analysis to predict healing after 12 weeks. The analysis revealed that only 33,3% of ulcers with P. aeruginosa, isolated at least once from 12 weeks prior, to or during surgery, were healed (98% or more) by week 12 follow-up, while 73,1% of ulcers without P. aeruginosa were so by the same time (p = 0,001). Smoking also significantly suppressed the outcome at the 12-week follow-up. Subsequently, a logistic regression analysis was carried out leaving P. aeruginosa as the only predictor left in the model (p = 0,001). This study supports our hypothesis that P. aeruginosa in chronic venous leg ulcers, despite treatment, has considerable impact on partial take or rejection of split-thickness skin grafts.     

Participation of mast cells in chronic otitis media

In the pathogenesis of chronic otitis media (COM), much attention is paid to the molecular mechanisms of local inflammatory reactions in which mast cells (MCs) may be involved due to their role not only in allergic but also inflammatory processes. The aim of this study was to assess the density of mast cells in chronic otitis media in relationship to different clinical courses of COM, bacterial infections and types of disease. The MCs expression was measured immunohistochemically in paraffin-embedded granulation tissue specimens taken during surgery, by staining with a monoclonal antibody against tryptase. The density of tryptase-positive mast cells was lower in tissue samples from the group with a good clinical course than in those from the group with poor healing and recurrence (p = 0.006). There were no differences between the groups of patients with granulomatous and cholesteatomatous chronic otitis media (p = 0.66) or between the groups of patients with and without bacterial infection (p = 0.30), although the density of mast cells was lower for those with Pseudomonas aeruginosa/Proteus sp./ /Staphylococcus MRSA infection. In conclusion, the expression of mast cells in chronic otitis media granulation tissue was found to differ depending on the clinical course of the disease, but not on bacterial infection or type of COM. This may suggest that mast cells contribute to the maintenance of the inflammatory process, but not to antibacterial defense in chronic otitis media.     

Genetic analysis of factor V Leiden in a family with history of thrombosis and venous leg ulcers

Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.     

Spatial distribution of venous gas emboli in the lungs.

The distribution of gaseous pulmonary emboli is presumed to be determined by their buoyancy. We hypothesized that regional pulmonary blood flow may also influence their distribution. Therefore, pulmonary blood flow was measured in supine, anesthetized dogs with use of 15-microm fluorescent microspheres at baseline and during N(2) embolism. The animals were killed, and the lungs were excised, air-dried, and diced into approximately 2-cm(3) pieces with weights and spatial coordinates recorded. Embolism was defined as a >10% flow decrease relative to baseline. Vertically, the incidence of embolism increased substantially by 6 +/- 1% per additional centimeter in height compared with baseline (P = 0.0003). Embolism also increased radially by 3 +/- 1%/cm from the hilum (P = 0.002). There was a weaker but statistically significant increase in embolism to pieces with greater baseline flow, 9 +/- 2% for every 1. 0 increase in relative baseline flow (P = 0.008). We conclude that the distribution of gaseous emboli is influenced by buoyancy and flow dynamics within the pulmonary vasculature.