Proliferation and mitogenic response to PDGF-BB of fibroblasts isolated from chronic venous leg ulcers is ulcer-age dependent.
Several pathophysiologic mechanisms have been proposed to explain slow-healing leg ulcers, but little is known about the growth behavior of cells in these wounds. Platelet-derived growth factor-BB applied topically to chronic wounds has shown beneficial effects, although the effects have been less pronounced than would have been expected based on studies on acute wounds. The objective of this study was to compare fibroblasts in culture obtained from chronic wounds (non-healing chronic venous leg ulcers), acute wounds and normal dermis regarding growth, mitogenic response to platelet-derived growth factor-BB and levels ofplatelet-derived growth factor alpha-receptor and beta-receptor. Fibroblasts were obtained by an explant technique and expanded in vitro using fibroblast growth medium supplemented with 10% fetal bovine serum and used for the assays at their third passage. Growth of chronic wound fibroblasts (n = 8) was significantly (p < 0.05) decreased compared with those from acute wounds (n = 10) and normal dermis (n = 5). Fibroblasts from ulcers older than 3 y grew significantly (p < 0.01) slower than those from ulcers that had been present for less than 3 y. Morphology and size of fibroblasts from the oldest chronic wounds deviated substantially from those of acute wounds and normal dermis, and resembled in vitro aged or senescent fibroblasts. Mitogenic response of chronic wound fibroblasts to human recombinant platelet-derived growth factor-BB was also reduced with ulcer age. No significant differences were found in the amount of either platelet-derived growth factor alpha-receptor or beta-receptor among the three groups. The features decreased growth related to ulcer age, altered morphology, and reduced response to platelet-derived growth factor, indicating that fibroblasts in some chronic wounds have approached or even reached the end of their lifespan (phase III). This might provide one explanation for the non-healing state and therapy resistance to topical platelet-derived growth factor-BB of some venous leg ulcers. (+info)
Risk factors for erysipelas of the leg (cellulitis): case-control study.
OBJECTIVE: To assess risk factors for erysipelas of the leg (cellulitis). DESIGN: Case-control study. SETTING: 7 hospital centres in France. SUBJECTS: 167 patients admitted to hospital for erysipelas of the leg and 294 controls. RESULTS: In multivariate analysis, a disruption of the cutaneous barrier (leg ulcer, wound, fissurated toe-web intertrigo, pressure ulcer, or leg dermatosis) (odds ratio 23.8, 95% confidence interval 10.7 to 52.5), lymphoedema (71.2, 5.6 to 908), venous insufficiency (2.9, 1.0 to 8.7), leg oedema (2.5, 1.2 to 5.1) and being overweight (2.0, 1.1 to 3.7) were independently associated with erysipelas of the leg. No association was observed with diabetes, alcohol, or smoking. Population attributable risk for toe-web intertrigo was 61%. CONCLUSION: This first case-control study highlights the major role of local risk factors (mainly lymphoedema and site of entry) in erysipelas of the leg. From a public health perspective, detecting and treating toe-web intertrigo should be evaluated in the secondary prevention of erysipelas of the leg. (+info)
The biomechanics of leg ulceration.
Research performed in the late 1960s, using 24Na, suggested that the perfusion of skin and subcutaneous tissues is critically dependent on the relationship between capillary (Pc) and tissue pressures (Pt). Perfusion changes differed significantly between controls and patients with venous disease and the differences could be interpreted as evidence that Pt remained high in venous diseased patients. From this starting point, a biomechanical theory for the aetiology of venous ulceration was developed and tested by measuring skin elasticity, limb cross-sectional area and laser Doppler flux. The results confirm that, modelled as a two-compartment system (vascular and interstitial fluid), forces can be demonstrated sufficient to cause intermittent capillary closure and subsequent reperfusion injury. These forces are maximal in the gaiter area, the site of most leg ulcers. (+info)
In vivo microscopic study of microcirculatory perfusion of the skin of the foot in peripheral vascular disease.
OBJECTIVES: the aim of this study was to determine the proportion of perfused capillaries in the skin of the foot in patients with peripheral vascular disease, and compare it with that in normal subjects. DESIGN: experimental study comparing capillary perfusion in nine patients with severe peripheral vascular disease (group 2) with seven age- and sex-matched control subjects (group 1). MATERIALS AND METHODS: using in vivo video microscopy, a method was developed to measure the ratio of perfused to total capillaries, by comparing the numbers of corresponding capillaries before and after intravenous injection of sodium fluorescein. RESULTS: the mean percentage ratio of perfused to total capillaries was 54.7% (range 41-87%, standard deviation 16.5) in group 1, and 86.0% (range 62-100%, standard deviation 13.2) in group 2 (p<0.001, t-test). CONCLUSION: a significantly higher proportion of capillaries is perfused in the skin of the foot of patients with severe peripheral vascular disease than in that of normal subjects. This is of important pathophysiological significance and may have clinical implications with regard to the role of pharmacological intervention in severe limb ischaemia. (+info)
Nontraumatic lower extremity amputations in the Medicare end-stage renal disease population.
BACKGROUND: Nontraumatic lower limb amputation is a serious complication of both diabetic neuropathy and peripheral vascular disease. Many people with end-stage renal disease (ESRD) suffer from advanced progression of these diseases. This study presents descriptive information on the rate of lower limb amputation among people with ESRD who are covered by the Medicare program. METHODS: Using hospital bill data for the years 1991 through 1994 from the Health Care Financing Administration's ESRD program management and medical information system (PMMIS), amputations were based on ICD9 coding. These hospitalizations were then linked back to the PMMIS enrollment database for calculation of rates. RESULTS: The rate of lower limb amputation increased during the four-year period from 4.8 per 100 person years in 1991 to 6.2 in 1994. Among persons whose renal failure was attributed to diabetic nephropathy, the rates in 1991 and 1994 were 11.8 and 13.8, respectively. The rate among diabetic persons with ESRD was 10 times as great as among the diabetic population at large. Two thirds died within two years following the first amputation. CONCLUSIONS: The ESRD population is at an extremely high risk of lower limb amputation. Coordinated programs to screen for high-risk feet and to provide regular foot care for those at high risk combined with guidelines for treatment and referral of ulceration are needed. (+info)
Randomised, double blind placebo controlled trial of pentoxifylline in the treatment of venous leg ulcers.
OBJECTIVE: To 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. DESIGN: Randomised, double blind placebo controlled trial, parallel group study of factorial design, permitting the simultaneous evaluation of alternative pharmaceutical, bandaging, and dressings materials. SETTING: Leg ulcer clinics of a teaching and a district general hospital in southern Scotland. PARTICIPANTS: 200 patients with confirmed venous ulcers and in whom other major causal factors were excluded. INTERVENTIONS: Pentoxifylline 400 mg three times daily or placebo. MAIN OUTCOME MEASURE: Complete healing (full epithelialisation) of all ulcers on the trial leg. RESULTS: Complete healing occurred in 65 of the 101 (64%) patients receiving pentoxifylline and 52 of the 99 (53%) patients receiving placebo. CONCLUSIONS: The difference in the healing rates between patients taking pentoxifylline and those taking placebo did not reach statistical significance. (+info)
Preliminary report of a toxicity study of hydroxyurea in sickle cell disease. French Study Group on Sickle Cell Disease.
AIM: To evaluate the tolerance of hydroxyurea in children affected with sickle cell disease. DESIGN: Questionnaire study of French physicians likely to treat patients with sickle cell disease. Data were collected on 101 children with sickle cell disease, treated for a median of 22 months, 36 of whom were treated for more than three years. 13 children were younger than 5 years of age at inclusion. RESULTS: Hydroxyurea was stopped for medical reasons in 11 patients: 6 failures, 1 pregnancy, 1 cutaneous rash, 1 leg ulcer, 1 lupus. Acute lymphoblastic leukaemia occurred in a girl treated for 1.5 months with hydroxyurea, this short interval arguing against a causative association. One 17 year old boy had paraparesis after 8 years of treatment. CONCLUSIONS: No major short or medium term toxicity was related to hydroxyurea in this cohort of 101 children. However, the number of children treated for more than 3 years is too few to make firm conclusions on the long term tolerance of this drug. (+info)
Mycobacterium ulcerans infection (Buruli ulcer): first reported case in a traveler.
A chronic, painless sore developed over a 2-month period on the left calf of a Canadian man traveling for 8 months in Africa. A presumptive diagnosis of a Mycobacterium spp. infection was made despite initially negative biopsy and culture results, after failure of several courses of anti-bacterial antibiotics. Mycobacterium ulcerans was eventually isolated and the lesion progressed despite treatment with multiple anti-mycobacterial agents. The lesion finally responded to wide and repeated excision, aggressive treatment with anti-mycobacterial antibiotics, and split-thickness skin grafting. The isolation and treatment of this unusual organism are discussed. (+info)