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PubMed1995

Cytokine and protease levels in healing and non-healing chronic venous leg ulcers.

Leg ulcers present a common and recurring problem in older people creating discomfort and distress for the patient and a great cost to the health care services. Cultured keratinocyte grafts have been used by many investigators to stimulate healing of chronic venous ulcers. It has been proposed that they may do this by producing cytokines which modulate the healing process. However, the types and levels of cytokines in the leg ulcer fluid before and during healing are not known. Wound fluid was collected from venous leg ulcers in 18 patients beneath occlusive Tegaderm dressing for 4 to 6 h. The leg ulcers were divided on clinical criteria into 'healing' and 'non-healing'. PDGF-AB, GM-CSF, IL-1 alpha, IL-1 beta, IL-6 and bFGF were measured by ELISA and the levels of IL-1 alpha, IL-1 beta and IL-6 were also measured using biological assays. The effect of leg ulcer wound fluid on fibroblast and keratinocyte proliferation was measured indirectly by 3H-thymidine incorporation and MTT assay. Total protein, albumin levels, fibronectin degrading activity and collagenase activity, both active and latent were measured. No statistically significant differences in the levels of cytokines or collagenase were identified between healing and non-healing leg ulcers in the sample of leg ulcers studied. However, this study does give valuable information concerning the levels of cytokines and collagenase in chronic leg ulcer wound fluid.

Aged↗
PubMed2004

Coordinated development of muscles and tendons of the Drosophila leg.

Since Miller's morphological description, the Drosophila leg musculature and its formation has not been revisited. Here, using a set of GFP markers and confocal microscopy, we analyse Drosophila leg muscle development, and describe all the muscles and tendons present in the adult leg. Importantly, we provide for the first time evidence for tendons located internally within leg segments. By visualising muscle and tendon precursors, we demonstrate that leg muscle development is closely associated with the formation of internal tendons. In the third instars discs, in the vicinity of tendon progenitors, some Twist-positive myoblasts start to express the muscle founder cell marker dumbfounded (duf). Slightly later, in the early pupa, epithelial tendon precursors invaginate inside the developing leg segments, giving rise to the internal string-like tendons. The tendon-associated duf-lacZ-expressing muscle founders are distributed along the invaginating tendon precursors and then fuse with surrounding myoblasts to form syncytial myotubes. At mid-pupation, these myotubes grow towards their epithelial insertion sites, apodemes, and form links between internally located tendons and the leg epithelium. This leads to a stereotyped pattern of multifibre muscles that ensures movement of the adult leg.

Animals↗
PubMed2001

Drosophila transcription factor AP-2 in proboscis, leg and brain central complex development.

We report loss- and gain-of-function analyses that identify essential roles in development for Drosophila transcription factor AP-2. A mutagenesis screen yielded 16 lethal point mutant alleles of dAP-2. Null mutants die as adults or late pupae with a reduced proboscis, severely shortened legs (approximately 30% of normal length) lacking tarsal joints, and disruptions in the protocerebral central complex, a brain region critical for locomotion. Seven hypomorphic alleles constitute a phenotypic series yielding hemizygous adults with legs ranging from 40-95% of normal length. Hypomorphic alleles show additive effects with respect to leg length and viability; and several heteroallelic lines were established. Heteroallelic adults have moderately penetrant defects that include necrotic leg joints and ectopic growths (sometimes supernumerary antennae) invading medial eye territory. Several dAP-2 alleles with DNA binding domain missense mutations are null in hemizygotes but have dominant negative effects when paired with hypomorphic alleles. In wild-type leg primordia, dAP-2 is restricted to presumptive joints. Ectopic dAP-2 in leg discs can inhibit but not enhance leg elongation indicating that functions of dAP-2 in leg outgrowth are region restricted. In wing discs, ectopic dAP-2 cell autonomously transforms presumptive wing vein epithelium to ectopic sensory bristles, consistent with an instructive role in sensory organ development. These findings reveal multiple functions for dAP-2 during morphogenesis of feeding and locomotor appendages and their neural circuitry, and provide a new paradigm for understanding AP-2 family transcription factors.

Alleles↗
PubMed2004

VenUS I: a randomised controlled trial of two types of bandage for treating venous leg ulcers.

OBJECTIVES: To compare the clinical and cost-effectiveness of two different compression bandages for the healing of venous leg ulcers. DESIGN: A pragmatic, randomised controlled trial with an economic evaluation. SETTING: Community, district nurse-led services; community leg ulcer clinics; hospital leg ulcer clinics with community outreach. A range of urban and rural settings in England and Scotland. PARTICIPANTS: Patients with a venous leg ulcer of at least 1-week's duration, at least 1 cm in length or width and an ankle:brachial pressure index of at least 0.8. INTERVENTIONS: The four-layer bandage (4LB) (which is multilayer elastic compression) compared with the short-stretch bandage (SSB) (multilayer, inelastic compression). MAIN OUTCOME MEASURES: The primary end-point was complete healing of all the ulcers on the trial leg. Secondary outcomes were the proportion of patients healed at 12 and 24 weeks, rate of recurrence, costs of leg ulcer treatment and quality of life. RESULTS: Between April 1999 and December 2000 the trial recruited 387 people aged from 23 to 97 years at trial entry. The majority of patients in this trial (82%; 316/387) had a reference ulcer of area </=10 cm(2). To test the difference over time of Kaplan--Meier curves for the two bandage groups, the distribution of the cumulative times to healing of individuals in the two trial groups was compared using the log-rank test. The difference in the distribution of cumulative healing times between the individuals in the two groups was not statistically significant at the 5% level. Adjusting for the effects of variables which may influence healing (centre, baseline ulcer area, duration, episodes, ankle mobility, weight) in a Cox proportional hazards model, a statistically significant treatment effect in favour of the 4LB was identified. At any point in time, the probability of healing for individuals in the SSB treatment arm is significantly lower than that for people treated with the 4LB. Our base case economic analysis showed that the 4LB is the dominant strategy, that is, it is associated with a greater health benefit and lower costs than the SSB, although the differences are not statistically significant. This result is explained largely by the greater number of community nurse visits required by participants in the short-stretch arm. CONCLUSIONS: The 4LB, which is currently the UK standard compression bandage for people with venous leg ulcers, was more clinically and cost-effective than the SSB. The bandage costs were less important than the costs of treatment visits, and patients in SSBs required more treatment overall. Generally, this trial supports the use of the 4LB in preference to the SSB. Recommendations for future research include: exploration of the relationship between bandager skill, application technique and ulcer healing; the relative cost-effectiveness of community leg ulcer clinics; and the study of nurse decision-making in venous ulcer management.

Adult↗
PubMed1975

The incidences of leg and foot abnormalities in Wrolstad White turkeys.

The leg and foot abnormalities of a flock of 911 Wrolstad White turkeys were described and were analyzed statistically to determine the relationship of the incidences of leg and foot abnormalities to sex and body weight of the turkeys. Body weight and a visual observation of the condition of legs and feet of each turkey were recorded at the age of nearly 12 weeks. The sex of each turkey had been recorded at one day of age. Based on chi-square contingency tables, the incidence of the leg and foot abnormalities was related to sex. The male turkeys were far more likely to experience leg and foot abnormalities than were the females. The incidence rate of severe leg and foot abnormalities was 16.1% for the males and 4.8% for females. The incidence of leg and foot abnormalities was not related to weight per se. The light turkeys of either sex were just as likely as the heavy turkeys of the same sex to have leg and foot abnormalities.

Animals↗
PubMed1991

Genetic association of selection for increased leg muscle and increased shank diameter with body composition and walking ability.

Body compositions of a randombred control population (RBC2), a line selected for increased 16-wk BW (F), a line selected for increased shank diameter (FL), and a line selected for increased leg muscle mass (FM) were compared at 16 wk of age. The F line originated from the RBC2 population and the FL and FM lines were developed as sublines of the F line. The F and FL lines were developed through mass selection of BW and shank width, respectively. The FM line was developed through family selection for leg muscle mass. Selection for BW in the F line has resulted in an increase in the proportion of breast muscle and a decrease in the relative amount of leg bone in comparison with the RBC2 population. Selection for increased shank width in the FL line has increased not only shank weight but has produced concomitant increases in the weight of the tibiotarsal and femur bones. Although FL line has also shown a correlated increase in BW in association with increases in shank width the increase in leg bone weight was relatively greater than the increase in BW. Therefore, the relative weights of leg bones in the FL line increased such that they were more similar to the RBC2 population than to the F line. Although the amount of leg muscle increased slightly in the FM line, the relative proportion of leg muscle did not increase significantly. The selection program used was probably ineffective in increasing the proportion of leg muscle because of the high percentage (low selection intensity) of families selected and small family size for estimating family means.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Osteochondrosis/osteoarthrosis and claw disorders in sows, associated with leg weakness.

The objective of this study was to investigate the associations between different leg weakness symptoms and osteochondrosis/osteoarthrosis and claw disorders in sows together with the influence of age on these findings. One hundred and seventeen sows in one herd were followed from 6 months of age until culling and judged for leg weakness once in every gestation using a scale from 1 (normal) to 4 (severe changes). At slaughter changes in joints, growth plates and claws were scored on a scale from 1 (normal) to 5 (very severe changes). Osteoarthrotic changes were strongly associated with osteochondral changes in humeral and femoral condyles. The clinical signs of osteochondrosis and osteoarthrosis were found to be: buck-kneed forelegs, turn out of fore and hind legs, upright pasterns on hind legs, stiff locomotion, lameness and tendency to slip. The clinical signs of claw lesions were found to be: buck-kneed forelegs, upright pasterns, steep hock joints, turn out of hind legs, standing under position on hind legs, stiff movements, swaying hindquarters, goose-stepping hind legs, tendency to slip and lameness. Overgrown claws were strongly associated with leg weakness indicating the need for claw trimming in sow populations.

Age Factors↗
PubMed1992

Intraarterial lymphocyte-injection therapy for lymphedema of the leg: an examination using indium-111 oxine labeled autologous lymphocytes.

A 58-year-old female patient with lymphedema of the left leg was treated by repeated intraarterial lymphocyte-injection therapy. To elucidate whether the injected lymphocytes act at the affected site of the leg, we examined the distribution of the In-111 oxine labeled lymphocytes injected into the proximal artery to the affected leg in comparison with the distribution in the other, healthy, leg. The radioactivity of the affected leg was almost two times higher than that of the healthy leg during the first 30 min after injection, and it remained higher even after 24 hours. The circumference of the affected leg of the patient decreased steadily during her hospital stay. These results, together with the clinical findings, suggest that some of the intraarterially-injected lymphocytes remained in the affected leg at least 24 hours and might play some role in reducing the volume of lymphedematous fluid.

Blood Component Transfusion↗
PubMed1986

The growth of supernumerary legs in the cockroach.

When the anteroposterior axis of a cockroach leg is reversed at a graft by exchanging a left leg for a right leg at the mid-tibia level, regeneration occurs in the region of the graft/host junction. This results in the formation of a pair of lateral supernumerary legs. In these experiments the patterns of cell division which take place during supernumerary leg formation were observed in sections of regenerating legs of the cockroach Leucophaea maderae. Early patterns of cell division resemble those seen in control grafts in which no axial reversal had been carried out during grafting. These cell divisions are associated with the process of wound healing. Later, a large area of the epidermis proximal to the graft/host junction becomes activated and shows a rapid rate of cell division. This area forms two outgrowths which grow by cell division throughout their epidermis to form the epidermis of the supernumerary legs. The results are more consistent with the view that the formation of supernumerary legs involves dedifferentiation of the epidermis in the region of the graft/host junction to form a blastema, rather than being due to local cell division at the point of maximum pattern discontinuity. This conclusion is used to offer an explanation for the range of different types of outcome of left-right grafts that has been observed.

Animals↗
PubMed1993

125I-fibrinogen leg scanning: reassessment of its role for the diagnosis of venous thrombosis in post-operative patients.

OBJECTIVE: To determine the reasons why 125I-fibrinogen leg scanning, a screening test which was reported to be very sensitive for the detection of post-operative thrombosis, has shown poor sensitivity in contemporary studies. STUDY IDENTIFICATION: English-language reports were identified through a Medline computer search (1965-1991), Current Contents, and an extensive manual search of the bibliographies in identified articles. STUDY SELECTION: Studies in orthopaedic or general surgical patients were reviewed that compared 125I-fibrinogen leg scanning with venography in all patients (accuracy studies) or in patients in whom 125I-fibrinogen leg scanning became positive (positive predictive value studies). DATA EXTRACTION: A systematic appraisal of study design and specific descriptive information concerning the selection of patients. RESULTS OF DATA SYNTHESIS: Six of the 15 studies which compared 125I-fibrinogen leg scanning with venography were level 1 studies (potential for bias minimized) and nine were classified as level 2 studies (potential for bias not minimized). In orthopaedic surgical patients, the pooled sensitivity of leg scanning for isolated calf vein thrombosis, for all venous thrombosis, and the pooled specificity were 55%, 45%, and 92% for the level 1 studies, respectively. These indices were 88%, 82%, and 79%, respectively for the level 2 studies (P < 0.001). Only two (level 2) studies were found that evaluated the accuracy of leg scanning for venous thrombosis in general surgical patients. CONCLUSION: We conclude that leg scanning is an insensitive method for the screening of post-operative venous thrombosis in orthopaedic patients. Our findings call into question the validity of the many studies (including meta-analyses) evaluating prophylactic agents for venous thrombosis which used leg scanning as the only test for the assessment of efficacy.

Fibrinogen↗
PubMed1996

Colour duplex ultrasonography in the rational management of chronic venous leg ulcers.

Colour duplex ultrasonographic imaging has largely replaced venography in the assessment of lower-limb venous disorders. This is a study of the use of duplex in the management of patients with chronic venous ulceration in community ulcer clinics. Patients with chronic leg ulceration and an ankle: brachial pressure index of 0.85 or greater were studied. Assessment of venous competence in both the deep and superficial systems of the affected and unaffected legs was performed using colour venous duplex imaging. Reflux was defined as reverse flow for greater than 1 s after manual calf compression. One hundred consecutive patients were assessed over 15 months. Of 111 ulcerated legs, 96 had active ulceration, while 15 had been ulcerated within the previous 6 months. Fifty-seven (51 per cent) of the 111 ulcerated legs had superficial incompetence alone (88 per cent long saphenous system or its perforators, 12 per cent short saphenous system). Six legs (5 per cent) had isolated deep venous incompetence. Forty-two legs had mixed superficial and deep venous reflux; 22 of these had undergone previous venous surgery. Colour venous duplex assessment demonstrated superficial venous disease in approximately half of limbs with chronic leg ulceration. Venous dysfunction in these patients is potentially curable by surgery.

Adult↗
PubMed2001

[Heterotopic replantation after bilateral lower leg amputation].

INTRODUCTION: Replantation is an established procedure in reconstructive surgery. In a bilateral lower leg amputation attempts should be made to rescue at least one extremity, if the patients' vital conditions are stable. PATIENT AND METHOD: We report on a patient who has suffered a bilateral lower leg amputation. Due to the complex injuries the left leg was heterotopically (cross-over) replanted to the right leg. At the left leg an above knee stump was created. In a second operation a soft tissue defect at the replanted extremity was covered by a free microvascular latissimus dorsi muscle flap. In addition, the tibial nerve was reconstructed. Thirteen months later the patient is able to walk with a prosthesis for his left leg and complete weight bearing of the replanted extremity. DISCUSSION: Indication for replantation depends on accompanying injuries and vital functions of the patient. Compared to a simple amputation a lower leg replantation prolongs hospital stay, delays mobilisation of the patient, and increases the necessary secondary procedures. However, after replantation functional outcome is mostly better than with prosthetic fitting, especially if reconstruction of sensation in the weight-bearing area is successful. Thus, in a bilateral amputation movement and stability, as well as quality of life, are improved by a replanted extremity.

Amputation Stumps↗
PubMed1996

Malignancy in chronic leg ulcers.

OBJECTIVE: To evaluate the frequency of malignant ulcers in patients presenting with leg ulcers. DESIGN: A descriptive study from data collected between July 1988 and June 1995 from 981 patients (2448 ulcers) attending a leg ulcer clinic. SETTING: A specialised leg ulcer clinic at a tertiary teaching hospital. SUBJECTS: 43 patients with 55 malignant skin lesions. OUTCOME MEASURES: Tissue biopsies in ulcerated lesions that suggested malignancy or were not responding to appropriate treatment. RESULTS: Forty-three patients were found to have malignant lesions on the legs, giving a frequency of malignant ulcers of 4.4 per 100 leg ulcer patients, or 2.2 per 100 leg ulcers. Seventy-five per cent of the malignant ulcers were basal cell carcinoma and 25% were squamous cell carcinoma. CONCLUSIONS: Malignant skin changes are common in chronic leg ulcers. A biopsy should be taken from all suspicious ulcers or ulcers that do not respond to appropriate treatment.

Aged↗
PubMed1991

Leg ulcer etiology--a cross sectional population study.

Three hundred eighty-two patients with active leg ulcers were clinically examined after random selection out of a population of 827 patients identified within a previous cross-sectional population survey. Bidirectional Doppler ultrasonography was used for objective assessment of arterial and venous circulation. The purpose was to register causative factors and the etiologic spectrum. Venous insufficiency was present in 332 (72%) of 463 legs with active ulceration; deep insufficiency occurred in 176 (38%), and purely superficial insufficiency was present in 156 (34%). Ankle/brachial index was 0.9 or less in 185 (40%) of ulcerated legs. Venous insufficiency was the dominating causative factor in 250 legs (54%), of which 60% was the result of deep venous insufficiency. Arterial insufficiency was judged to be the possible dominating factor in 12%, and 6% showed clearly ischemic ulcers. Mixed ulcers with combined arterial and venous insufficiency were found to be common as were patients with diabetes and arterial impairment. In 10% of the legs a multifactorial origin was present, and in 10% no venous or arterial impairment was detectable. Thus after classification of causes 40% of all ulcerated legs showed potentially surgically curable circulatory disturbances. It is necessary to objectively assess all patients with chronic leg ulcers to be able to detect patients with potentially surgically curable disease.

Adolescent↗
PubMed1998

Predicting healing of arterial leg ulcers by means of segmental systolic pressure measurements.

BACKGROUND: The Second European Consensus Document on Chronic Critical Leg Ischemia defined criteria to predict healing of leg ulcers. These recommendations are based on selected studies but the true performances of the tests proposed are not stated. METHODS: We performed an electronic and manual literature search to retrieve all studies that included the comparison of clinical outcome of cutaneous arterial leg ulcers with ankle (AP) and toe (TP) systolic pressures and we calculated the sensitivity and specificity of these measurements for predicting ulcer healing, according to standard methods for proportions and ROC curve analysis. RESULTS: Only three studies totalizing 220 legs with cutaneous ulcers (> 50% of the patients had diabetes) fulfilled our predefined criteria. The best performances of the tests (defined as the maximal area under the ROC curve) were obtained for an AP and a TP of 80 mmHg and 30 mmHg, respectively. Our analysis suggests that an AP > or = 80 mmHg predicts a favorable outcome with healing of leg ulcers. This simple test can be performed by the general practitioner. An AP of 50-80 mmHg should be followed by a TP and/or a transcutaneous PO2 measurement in case of unfavorable evolution. CONCLUSION: Our study confirms objectively the clinical validity of the criteria (AP < or = 50 mmHg, TP < or = 30 mmHg) supported by the Second European Consensus Document on Chronic Critical Leg Ischemia to predict unfavorable outcome of cutaneous arterial leg ulcers and provides objective performance values for these measurements.

Blood Gas Monitoring, Transcutaneous↗
PubMed1999

Exertional leg symptoms other than intermittent claudication are common in peripheral arterial disease.

BACKGROUND: Epidemiological data show that most community-dwelling men and women with lower-extremity peripheral arterial disease (PAD) do not have typical symptoms of intermittent claudication. We compared the prevalence of intermittent claudication, leg symptoms other than intermittent claudication, and absence of exertional leg symptoms between patients with PAD identified from a blood flow laboratory (group 1), patients with PAD in a general medicine practice (group 2), and control patients without PAD (group 3). METHODS: Numbers of participants in groups 1, 2, and 3 were 137, 26, and 105, respectively. Patients with previously diagnosed PAD were excluded from groups 2 and 3. All participants underwent ankle-brachial index measurement and were administered the San Diego claudication questionnaire to assess leg symptoms. RESULTS: Within groups 1, 2, and 3, prevalences of intermittent claudication were 28.5% (n = 39), 3.8% (n = 1), and 3.8% (n= 4), respectively. Prevalences of exertional leg symptoms other than intermittent claudication were 56.2% (n= 77), 42.3% (n= 11), and 19.0% (n = 20), respectively. Absence of exertional leg symptoms was reported by 15.3% (n= 21), 53.8% (n= 14), and 77.1% (n=81), respectively. Among patients with PAD, older age, male sex, diabetes mellitus, and group 2 vs group 1 status were associated independently with absence of exertional leg symptoms in multivariable regression analysis. Lower ankle-brachial index levels and group 1 vs group 2 status were associated with intermittent claudication. CONCLUSIONS: Clinical manifestations of PAD are diverse, particularly among patients identified by ankle-brachial index screening. Exertional leg symptoms other than intermittent claudication are common in PAD. Patients with PAD who are older, male, diabetic, or identified with ankle-brachial index screening in a primary care setting are more likely to have asymptomatic PAD.

Age Factors↗
PubMed1990

Variable expressivity in familial restless legs syndrome.

A 62-year-old man with a 20-year history of excessive daytime somnolence and kicking during sleep was an obligate carrier of the restless legs syndrome gene because his paternal grandfather, father, and all three of his children had symptoms of restless legs syndrome. The patient himself, however, denied motor restlessness after a careful and exhaustive medical history and he was originally believed to have periodic movements in sleep without restless legs. Close clinical observation did reveal nighttime motor restlessness, although the patient continued to deny its importance. Polysomnography showed frequent periodic movements in sleep. We conclude that there can be variable expressivity of the clinical features in familial restless legs syndrome and that there are probably some relatively nonrestless patients with prominent periodic movements in sleep who are carriers of the restless legs syndrome gene. Some sleep-disordered patients who are believed to have only periodic movements in sleep may have a forme fruste of autosomal dominant restless legs syndrome. If one does not examine these patients carefully at night and take an adequate family history, one may miss the diagnosis of restless legs syndrome.

Gene Expression↗
PubMed2007

Diagnostic indicators of restless legs syndrome in primary care consultations: the DESYR study.

The objective of this study is to determine whether spontaneous complaints about sleep or the legs could be used as potential indicators of restless legs syndrome (RLS) in primary care. A total of 351 general practitioners participated in the study. In a first historical patient identification phase, all patients with spontaneous complaints of sleep or leg symptoms over the previous year were identified. A control group without such complaints was identified. In a second prospective data collection phase, those who consulted a participating physician were interviewed to assess consensus diagnostic criteria of RLS. Severity was assessed with the International Restless Legs Syndrome Study Group severity rating scale. Of 1,405,823 patients consulting during the historical phase, a leg complaint was reported in 61,685 and a sleep complaint in 40,568. A total of 1,432 consulted during the prospective phase. A diagnosis of RLS was assigned to 42.6% of patients with leg complaints, 35.5% of those with sleep complaints, 54.9% of those with both complaints, and 12.9% of those with no complaints. Median RLS severity scores were 18.8 to 20.4. A total of 63.7% of patients were prescribed a venotonic, 43.7% a hypnotic, and 41.5% an anxiolytic. Complaints of sleep or leg symptoms are frequently associated with a diagnosis of RLS, and their presence should alert the physician to the possibility of a differential diagnosis of RLS.

Adult↗